Friday, June 18, 2010

Abstract: Sjogrens vs. MS

[Sjögren's Syndrome or Multiple Sclerosis? A dilemma in clinical practice]
Acta Reumatol Port. 2010 Jan-Mar;35(1):60-4.
[Article in Portuguese]
Duarte C, Teotónio R, Abreu P, Dias P, Matias F.
Serviço de Reumatologia, Hospitais da Universidade de Coimbra, Coimbra.

The authors present a clinical case of a male, 53-years old with a multiple sclerosis like syndrome, progressive, with 3 years of evolution. The patient also referred dry eye and inflammatory arthralgias, the complementary workup was according with Sjögren's Syndrome. The central nervous system involvement of Sjögren's Syndrome and the difficulty of differential diagnosis with neurological diseases such as Multiple sclerosis is discussed.

Abstract: Effect of eyedrop instillation on optical quality...

Of course we see better briefly after putting in drops. So what? Why have there been so many studies published about it? Yawn...

Optical quality after instillation of eyedrops in dry-eye syndrome.
J Cataract Refract Surg. 2010 Jun;36(6):935-40.
Montés-Micó R, Cerviño A, Ferrer-Blasco T, García-Lázaro S, Ortí-Navarro S.
Optometry Research Group, Faculty of Physics, University of Valencia, Valencia, Spain.

PURPOSE: To study the effect of eyedrop instillation on the optical quality of the air-tear film interface at the anterior cornea in cases of dry eye.

SETTING: University of Valencia, Valencia, Spain.

METHODS: Corneal aberrations (total, spherical-like, and coma-like) were determined from corneal elevation maps and purpose-designed software in cases of dry eye before, immediately after, and 10 minutes after lubricating eyedrop instillation (Blink Intensive Tears). All data were decomposed using Zernike polynomials to yield the root-mean-square wavefront deviations for pupil diameters of 3.0 mm and 5.5 mm. Outcome measures included comparison with clinical tear breakup time (TBUT).

RESULTS: Wavefront higher-order aberrations (HOAs) decreased significantly, by a factor of 2.5 on average, after artificial tear instillation with both pupil diameters (P<.01). The reduction was maintained 10 minutes after eyedrops instillation (P>.2). The mean TBUT was 3.6 seconds +/- 1.7 (SD). Eyedrop instillation increased the TBUT values significantly (by approximately 60%) from baseline (P<.01).

CONCLUSIONS: This method of air-tear film interface analysis facilitated evaluation of optical quality improvement after eyedrop instillation in patients with dry eye. After eyedrops were given, the increasingly regular tear film decreased HOAs, improving optical quality.

Abstract: The effect of iodide iontophoresis on the antioxidative capacity of the tear fluid

The effect of iodide iontophoresis on the antioxidative capacity of the tear fluid.
Graefes Arch Clin Exp Ophthalmol. 2010 May 23. [Epub ahead of print]
Rieger G, Klieber M, Schimetta W, Pölz W, Griebenow S, Winkler R, Horwath-Winter J, Schmut O, Spitzer-Sonnleitner B.
Paracelsus Society for Balneology and Iodine Research, Kurpromenade 1, 4540, Bad Hall, Austria,

BACKGROUND: Environmental oxidative stress changing the properties of the tear fluid can lead to keratoconjunctivitis sicca (dry eye syndrome). The aim of this study was to determine whether iodide iontophoresis influences the antioxidative capacity (ACW = water soluble antioxidative capacity) of the tear fluid, and to compare iodide iontophoresis with other balneotherapeutic measures.

METHODS: This prospective study evaluated 92 patients in four groups. Twenty-four patients were treated with iodide iontophoresis, 24 with other balneotherapeutic methods. Twenty-five patients received iodide iontophoresis combined with other balneotherapeutic methods and 21 persons received no treatment (control). Unstimulated tear fluid, serum and urine were collected. ACW was determined photochemically in tear fluid and serum; iodine was measured in urine photometrically.

RESULTS: Iodide iontophoresis increases the ACW of the tear fluid but not the ACW of the serum. Other iodine therapies increase the ACW in serum but not in tear fluid. Iodine excretion in urine was increased in all treated groups compared to the control.

CONCLUSION: The increase of ACW in tear fluid after iodide iontophoresis can support the defense mechanism of the eye against oxidative influence effects, which may alleviate the symptoms of keratoconjunctivitis sicca.

Abstract: Salivary gland transplantation for severe dry eye from chemical burns and SJS

Labial salivary gland transplantation for severe dry eye due to chemical burns and Stevens-Johnson syndrome.
Ophthal Plast Reconstr Surg. 2010 May-Jun;26(3):182-4.
Marinho DR, Burmann TG, Kwitko S.
Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Federal University of RGS, Porto Alegre, Brazil.

PURPOSE: Salivary gland transplantation has been a promising alternative for the treatment of dry eye syndrome. In this article, we describe the results of an autotransplant procedure of labial salivary glands in the upper conjunctival fornix of patients with severe dry eye.

METHODS: A total of 14 eyes from 14 patients presenting with Stevens-Johnson syndrome and chemical burns were prospectively analyzed after surgery (average follow-up of 14 months). We evaluated their underlying symptoms, visual acuity, biomicroscopy, Schirmer's test, break-up time, and need for lubricants before and after transplantation.

RESULTS: All patients expressed improvement in their ocular discomfort. Nine eyes showed a slight best-corrected visual acuity improvement, while the vision of the remainder stayed stable. Corneal staining, present in all patients before surgery, was persistent in only four patients, but in a reduced area. Schirmer's test and break-up time showed significant increase in all patients (p < 0.05). In 71% of the patients, the use of lubricants was reduced.

CONCLUSION: Labial salivary gland transplantation can improve the life quality of patients with compromised ocular surfaces who suffer from severe dry eye syndrome.

Abstract: Floppy eyelid syndrome... and other lax eyelid conditions

Floppy eyelid syndrome as a subset of lax eyelid conditions: relationships and clinical relevance (an ASOPRS thesis).
Ophthal Plast Reconstr Surg. 2010 May-Jun;26(3):195-204.
Fowler AM, Dutton JJ.
Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina 27599-7040, USA.

PURPOSE: To better define the wide spectrum of lax eyelid conditions, especially the subtype referred to as floppy eyelid syndrome, and to clarify its relationship with associated ophthalmic findings.

METHODS: A case-based retrospective review of all patients seen at UNC Department of Ophthalmology with a diagnosis of floppy eyelid syndrome or lax upper eyelid was performed. The period of review was from March 2002 to March 2007. A literature review was also performed using the term "floppy eyelid syndrome" and "lax eyelid syndrome" as the keywords in a PubMed search. Charts and cases were reviewed for the following information: age, sex, presence or absence of obesity, presence or absence of upper eyelid laxity, presence or absence of lower eyelid laxity, symmetry or asymmetry of eyelid laxity, sleeping position preference, diagnosis of obstructive sleep apnea (OSA), history of eye rubbing, diagnosis of keratoconus (KCN), lash ptosis, history of spontaneous eyelid eversion, papillary conjunctivitis, systemic hyperlaxity, diagnosis of meibomianitis, signs of anterior segment inflammation, and smoking or excessive sun exposure history.

RESULTS: From our UNC case review, 14 patients involving 17 eyelids were identified. From the literature review, 72 articles were recovered and evaluated to yield a total of 324 reported cases through February 2007. From the combined data (n = 338), the overall minimum prevalence of sleep apnea in patients with lax eyelid condition was 16% compared with an estimated 9% to 24% in the general population. Of patients with lax eyelid syndrome, those identified with OSA had significantly more individuals with obesity (76% vs. 20%) and male gender (89% vs. 61%) than the group without OSA. The prevalence of KCN in patients with lax eyelid syndrome was a minimum of 6.8%, which is considerably higher than the estimated prevalence in the general population of 0.6%. However, KCN appears to show a significant association with the patient's side of sleeping preference.

CONCLUSIONS: Eyelid laxity can result from a number of involutional, local, and systemic diseases but is frequently of unknown etiology. When it is consistently associated with papillary conjunctivitis and dry eyes it can be referred to as lax eyelid syndrome (LES). A number of specific subsets of LES can be identified. One such subset, occurring primarily though not exclusively in males and associated with obesity, has been defined as the floppy eyelid syndrome (FES). OSA has been associated with FES where it occurs with greater frequency than in the general population, but no greater than seen in obese males without FES, and therefore appears to represent an epiphonomenom only. However, given the demographics of FES, this condition offers some predictive value for OSA and should alert the physician to evaluate the sleep habits of all such patients. Keratoconus also shows some association with FES and with LES. However, data suggest that the causative factors are sleep preference for the involved side and nocturnal eyelid eversion, rather than any underlying physiologic or anatomic relationship.

Abstract: Azasite for MGD

Topical Azithromycin Therapy for Meibomian Gland Dysfunction: Clinical Response and Lipid Alterations.
Cornea. 2010 May 20. [Epub ahead of print]
Foulks GN, Borchman D, Yappert M, Kim SH, McKay JW.
From the *Departments of Ophthalmology and Vision Science; and daggerChemistry, University of Louisville, Louisville, KY.

PURPOSE:: Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease and spectroscopic behavior of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution.

METHODS:: Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid, lipid-lipid interaction strength, and conformation and phase transition parameters were measured using Fourier transform infrared spectroscopy.

RESULTS:: In subjects with clinical evidence of MGD, changes in ordering of the lipids and resultant alteration of phase transition temperature were identified. Topical therapy with azithromycin relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal.

CONCLUSIONS:: Improvement in phase transition temperature of the meibomian gland lipid with the determined percent trans rotomer composition of the lipid strongly suggests that the ordering of the lipid molecules is altered in the disease state (MGD) and that azithromycin can improve that abnormal condition toward normal in a manner that correlates with clinical response to therapy.

Abstract: A new lipid tear (mouse study)

A lot of unanswered questions here that I hope are addressed in the study... such as what sodium hyaluronate product that was.

Effects of a New Lipid Tear Substitute in a Mouse Model of Dry Eye.
Cornea. 2010 May 20. [Epub ahead of print]
Scifo C, Barabino S, De Pasquale G, Blanco AR, Mazzone MG, Rolando M.
From the *Business Unit Pharma S.I.F.I. Spa Via E. Patti 36, Lavinaio, Aci S. Antonio (Catania), Italy; and daggerOcular Surface Research Center, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Viale Benedetto, Genoa, Italy.

PURPOSE:: The present investigation is aimed to evaluate the effect of a new lipid artificial tear on tear volume and ocular surface signs in a mouse model of dry eye and to test the hypothesis that the combined application with sodium hyaluronate can improve the performance of the treatments.

METHODS:: A new oil-in-water emulsion, a 0.2% sodium hyaluronate solution, or their combined administration were given to dry eye mice maintained in a controlled environment chamber and treated with scopolamine (0.75-mg transdermal patch). Mice were treated 4 times a day with (a) sodium hyaluronate, (b) emulsion, and (c) sodium hyaluronate followed by emulsion. A control group of mice exposed to controlled environment chamber remained untreated (CTRL+). Tear volume and corneal damage were assessed after 3 and 7 days of treatment by cotton thread test and fluorescein staining.

RESULTS:: As regards tear volume, sodium hyaluronate did not show a statistically significant effect at either end point; the emulsion was effective after 7 days, whereas their combined administration counteracted the lacrimal decrease induced by the model both at 3 and 7 days. Corneal damage was reduced in all treated groups with respect to CTRL+. This effect was statistically significant after 3 days when the emulsion alone or in combination with sodium hyaluronate was used, while hyaluronate improved this clinical sign after 7 days.

CONCLUSIONS:: Our data suggest that the new lipid tear substitute can be used to treat clinical signs of dry eye and that the combined administration with hyaluronate can decrease the lag time before the effect, when the evaporative and the aqueous-deficient components are present.

Abstract: Ocular GVHD after allogeneic stem cell transplantation

Ocular Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation.
Cornea. 2010 May 20. [Epub ahead of print]
Westeneng AC, Hettinga Y, Lokhorst H, Verdonck L, van Dorp S, Rothova A.
From the *Departments of Ophthalmology; and daggerHematology, University Medical Center Utrecht, Utrecht, The Netherlands.

PURPOSE:: To determine the prevalence and manifestations of ocular graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (allo-SCT).

METHODS:: Prospective study of 101 consecutive patients who received allo-SCT from 2004 to 2007. All patients received ophthalmologic examination for 3 months after allo-SCT, and those with ocular complaints were evaluated at 12 and 24 months thereafter. We registered ophthalmologic and hematological data, including the indication for allo-SCT, occurrence of systemic and ocular GvHDs, ocular manifestations, and various ocular treatments.

RESULTS:: Over time, ocular GvHD developed in 54% of patients and consisted mainly of dry eyes and conjunctivitis, which increased in severity during follow-up; blepharitis and uveitis were less often encountered. Acute systemic GvHD, especially the involvement of mouth and skin, was strongly associated with ocular GvHD at 3 months (P = 0.000). Chronic GvHD was associated with the occurrence of ocular GvHD (P = 0.000), especially with the development of the dry eye. Although eye symptoms affecting activities of daily living were reported in 24 of 54 patients (44%) and 16 of 54 patients (30%) experienced temporary loss of visual acuity of more than 2 Snellen lines, only 1 developed permanent unilateral loss (counting fingers) because of ischemic vasculopathy. Cataract development was not encountered, and only 1 eye developed intraocular infection.

CONCLUSION:: Ocular GvHD develops in a substantial part of patients after allo-SCT and decreases the activities of daily living.

Abstract: A Clinical Alternative to Fluorophotometry for Measuring Tear Production in the Diagnosis of Dry Eye

A Clinical Alternative to Fluorophotometry for Measuring Tear Production in the Diagnosis of Dry Eye.
Cornea. 2010 May 20. [Epub ahead of print]
McCann LC, Tomlinson A, Pearce EI, Khanal S, Kaye SB, Fisher AC.
From the *Department of Vision Sciences, Glasgow Caledonian University, Glasgow, United Kingdom; daggerSt. Paul's Eye Unit; double daggerDepartment of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, United Kingdom; and section signSchool of Natural Sciences, University of Western Sydney, New South Wales, Australia.

PURPOSE:: To determine the utility of the tear function index (Liverpool modification TFI) in assessing tear turnover rate (TTR), evaluate association of tear clearance rate (TCR) and TFI with measurements of TTR by fluorophotometry, and determine effectivity of these test measures in dry eye (DE) diagnosis.

METHODS:: Forty-one subjects with DE and 15 control subjects participated. Tests included symptoms, fluorophotometry (by automated scanning fluorophotometry), and TCR and TFI from a prepared Liverpool modification TFI strip.

RESULTS:: Significant differences between subjects with DE and control subjects were found for all tests. Although wetting length values gave highest sensitivity (SS) and specificity (SP) (71% and 73%, respectively), this resulted from a high degree of selection bias because the Schirmer test was one of the inclusion criteria for patients entering the study. Therefore, the best tear production test was found to be TTR (SS 71% and SP 60%). The TTR test is not readily available in clinical settings; therefore, associations between the TTR test and other tests were determined. Significant correlations were found between TTR and wetting length/TCR/TFI, indicating these latter clinical tests useful as surrogates. The strongest correlations, TTR/TCR at 0.69 (P = 0.000) and TTR/TFI at 0.65 (P = 0.000), indicate TCR/TFI with the Liverpool test can be used as an alternative to TTR by fluorophotometry. The diagnostic effectiveness between these tests was compared, with both TCR and TFI found to have equal effectivity of 78% SS and 40% SP (TCR) and 83% SS and 40% SP (TFI).

CONCLUSIONS:: TCR measured by the commercially available Liverpool modification TFI strip is an acceptable alternative to TTR by fluorophotometry as a measure of tear production. It is effective as a single test for the discrimination of those with DE from those without the condition.

Abstract: Impact of symptomatic dry eye on vision-related daily activities

Impact of symptomatic dry eye on vision-related daily activities: The Singapore Malay Eye Study.
Eye (Lond). 2010 May 21. [Epub ahead of print]
Tong L, Waduthantri S, Wong TY, Saw SM, Wang JJ, Rosman M, Lamoreux E.
[1] Singapore National Eye Center, Singapore [2] Singapore Eye Research Institute, Singapore.

Purpose: To examine the impact of symptomatic dry eye on vision-related daily activities.

Methods: A population-based survey of eye diseases was conducted on 3280 (78.7% response rate) Malay persons aged >/=40 years, who were randomly selected from designated areas in southwestern Singapore. Participants were administered a standardized dry eye questionnaire consisting of six questions on symptoms, a questionnaire on vision-related daily activities, and underwent a comprehensive systemic and ocular examination. Symptomatic dry eye was defined as one or more self-reported symptoms that were frequently present (ranked as often or all the time). Logistic regression method was used to examine the relationship of symptomatic dry eye with difficulty in performing daily activities.

Results: In adults without visual impairment, symptomatic dry eye after adjusting for age, gender, and presenting visual acuity was significantly associated with difficulty in vision-related activities such as navigating stairs (odds ratio (OR)=1.96, 95% confidence interval (CI): 1.28-3.00), recognizing friends (OR=1.99, 95% CI: 1.45-2.73), reading road signs (OR=1.87, 95% CI: 1.36-2.57), reading newspaper (OR=1.50, 95% CI: 1.11-2.04), watching television (OR=1.90, 95% CI: 1.26-2.87), cooking (OR=1.94, 95% CI: 1.02-3.71), and driving at night (OR=2.06, 95% CI: 1.32-3.21).

Conclusion: Symptomatic dry eye was associated with difficulty in performing vision-dependent tasks, independent of visual acuity and other factors. These findings have public health significance and suggest that the visual dysfunction in dry eye should be further characterized.Eye advance online publication, 21 May 2010; doi:10.1038/eye.2010.67.

Abstract: TFF3

Trefoil Factor Family Peptide 3 at the Ocular Surface. A Promising Therapeutic Candidate for Patients with Dry Eye Syndrome?
Dev Ophthalmol. 2010;45:1-11. Epub 2010 May 18.
Schulze U, Sel S, Paulsen FP.
Departments of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.

Dry eye syndrome is a widespread disease accompanied by discomfort and potential visual impairments. Basic causes are tear film instability, hyperosmolarity of the tear film, increased apoptosis as well as chronic inflammatory processes. During the last decades, our understanding of dry eye syndrome has considerably increased. However, the molecular mechanisms of the disease remain largely elusive. In this context, our group focuses on trefoil factor 3 (TFF3). Among other factors, TFF3 performs a broad variety of protective functions on surface epithelium. Its main function seems to be in enhancing wound healing by promoting a process called 'restitution'. Studies evaluating TFF3 properties and effects at the ocular surface using in vivo as well as in vitro models have revealed a pivotal role of TFF3 in corneal wound healing. Subsequent studies in osteoarthritic cartilage seem to draw a different picture of TFF3, which still needs further elucidation. This manuscript summarizes the findings concerning TFF3 in general and its role in the cornea as well as articular cartilage - two tissues which have some things in common. It also discusses the potential of TFF3 as a candidate therapeutic agent for the treatment of, for example, ocular surface disorder

Abstract: Cationic Amino Acid Transporters and beta-Defensins in Dry Eye Syndrome

Cationic Amino Acid Transporters and beta-Defensins in Dry Eye Syndrome.
Dev Ophthalmol. 2010;45:12-15. Epub 2010 May 18.
Jäger K, Garreis F, Dunse M, Paulsen FP.
Department of Anatomy and Cell Biology, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany.

Several diseases concomitant with L-arginine deficiency (diabetes, chronic kidney failure, psoriasis) are significantly associated with dry eye syndrome. One important factor that has so far been neglected is the y(+) transporter. In humans, y(+) accounts for nearly 80% of arginine transport, exclusively carrying the cationic amino acids L-arginine, L-lysine and L-ornithine. y(+) is represented by CAT(cationic amino acid transporter) proteins. L-arginine is a precursor of the moisturizer urea, which has been used in the treatment of dry skin diseases. Although urea has also been shown to be part of the tear film, little attention has been paid to it in this role. Moreover, L-arginine and L-lysine are major components contributing to synthesis of the antimicrobially active beta-defensins induced under dry eye conditions. The first results have demonstrated that transport of L-arginine and L-lysine into epithelial cells is limited by the y(+) transporter at the ocular surface. Copyright © 2010 S. Karger AG, Basel.

Tuesday, June 15, 2010

Abstract: Antimicrobial peptides and the ocular surface's immune defense

Antimicrobial Peptides as a Major Part of the Innate Immune Defense at the Ocular Surface.
Dev Ophthalmol. 2010;45:16-22. Epub 2010 May 18.
Garreis F, Gottschalt M, Paulsen FP.
Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.

The ocular surface is in constant contact with the environment (e.g. when using one's fingers to insert a contact lens) and thus also with diverse bacteria, bacterial components and their pathogen associated molecules. Dysfunctions of the tear film structure or decreased moistening of the ocular surface, as in dry eye (keratoconjunctivitis sicca) for example, often lead to inflammatory and infectious complications resulting in severe functional disorders, particularly concerning the cornea. Besides different protective antimicrobial substances in the tear fluid (mucins, lysozyme, lactoferrin), the epithelia of cornea and conjunctiva can also protect themselves from microbial invasion by producing an arsenal of antimicrobial peptides (AMPs). A number of different studies have revealed that small cationic AMPs, which display antimicrobial activity against a broad spectrum of microorganisms, are a major component of the innate immune system at the human ocular surface. Furthermore, several AMPs modulate cellular activation processes like migration, proliferation, chemotaxis and cytokine production, and in this way also affect the adaptive immune system. In this article, we have summarized current knowledge of the mechanisms of activity and functional roles of AMPs, with a focus on potential multifunctional roles of human beta-defensins and S100 peptide psoriasin (S100A7) at the ocular surface.

Abstract: Regulation of the Inflammatory Component in Chronic Dry Eye Disease by the EALT

I would love to see those schematics....

Regulation of the Inflammatory Component in Chronic Dry Eye Disease by the Eye-Associated Lymphoid Tissue (EALT).
Dev Ophthalmol. 2010;45:23-39. Epub 2010 May 18.
Knop N, Knop E.
Department of Cell Biology in Anatomy, Hannover Medical School, Hannover, Germany.

Purpose: The physiologically protective mucosal immune system of the ocular surface consists of lymphocytes, accessory leukocytes and soluble immune modulators. Their involvement has also been observed in inflammatory ocular surface diseases, including dry eye syndrome, and we have attempted here to describe their interaction.

Methods: Our own results regarding the mucosal immune system of the human ocular surface are discussed together with the available literature on mucosal immunity and inflammatory ocular surface disease.

Results: The mucosa of the ocular surface proper (conjunctiva and cornea) is anatomically continuous with its mucosal adnexa (the lacrimal gland and lacrimal drainage system) and contains a mucosal immune system termed 'eye-associated lymphoid tissue' (EALT). This extends from the periacinar lacrimal-gland-associated lymphoid tissue along the excretory ducts into the conjunctiva-associated lymphoid tissue (CALT) and further into the lacrimal drainage-associated lymphoid tissue (LDALT). EALT consists of continuous diffuse lymphoid effector tissue and of interspersed follicles for effector cell generation in CALT and LDALT. Typical events in ocular surface disease include alteration and activation of epithelial cells with loss of epithelial integrity, production of inflammatory cytokines, and potential presentation of non-pathogenic and self-antigens - leading to a loss of immune tolerance. Events in the deregulation of physiologically protective EALT, resulting vicious circles, and eventual self-propagating immunomodulated inflammatory disease processes are explained, discussed and visualized by schematic drawings.

Conclusion: Deregulation of EALT can orchestrate a self-propagating inflammatory mucosal disease process if the capacity of natural compensatory factors is overridden and if the disease is not limited by timely diagnosis and therapy.

Copyright © 2010 S. Karger AG, Basel.

Abstract: Tissue engineering & lacrimal gland reconstruction

Wow. This is definitely a research group the chronic MGD crowd need to keep an eye on. And in London, of all the unlikely places to generate serious dry eye research.

Very interesting.

Generation of Two- and Three-Dimensional Lacrimal Gland Constructs.
Dev Ophthalmol. 2010;45:49-56. Epub 2010 May 18.
Schrader S, Liu L, Kasper K, Geerling G.
Cells for Sight Transplantation and Research Programme, Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, London, UK.

Aqueous tear deficiency due to lacrimal gland insufficiency is one of the major causes of dry eye. In severe cases, such as Sjoegren's syndrome, Stevens-Johnson syndrome or ocular cicatricial pemphigoid, therapy with artificial tears can be insufficient to relieve severe discomfort. Engineering a lacrimal gland construct may offer a suitable alternative transplant with a tear-like secretion. However, the reconstruction of a complex structure such as the lacrimal gland is challenging, and a lacrimal gland substitute must meet several criteria. It has to contain enough functional lacrimal gland cells to produce an adequate amount of tear fluid, and a suitable matrix is needed to deliver the cells to the patient. The growing field of regenerative medicine offers promising new prospects for lacrimal gland reconstruction. This article summarizes our group's current work in developing models for lacrimal gland reconstruction, and also discusses the perspectives of a tissue-engineered lacrimal gland for future applications. Copyright © 2010 S. Karger AG, Basel.

Abstract: Modifying a dry eye model

Towards a New in vitro Model of Dry Eye: The ex vivo Eye Irritation Test.
Dev Ophthalmol. 2010;45:93-107. Epub 2010 May 18.
Spöler F, Frentz M, Schrage NF.
Institute of Semiconductor Electronics, RWTH Aachen University, Aachen, Germany.

Understanding of dry eye syndrome (DES) today is driven by in vivo analysis of tear osmolarity, tear film break up time, impression cytology and description of symptoms. Existing in vivo models of DES need severe alterations of tear production or corneal integrity. For a more detailed analysis of DES under particular environmental and treatment conditions a considerable lack of in vitro methods exists. The main disadvantage of current in vitro models is the limited experimental time frame of only several hours and the impossibility to evaluate healing of epithelial defects. In the present study, evidence is given that these restrictions can be overcome by modifying the established Ex Vivo Eye Irritation Test (EVEIT) to realize a model system for DES. This test is based on abattoir rabbit eyes allowing an experimental time frame of up to 21 days using self-healing corneal cultures. In first experiments it is demonstrated that different severity levels of dry eye can be simulated in the EVEIT system. High-resolution optical coherence tomography (OCT) is applied to monitor the initial phase of DES under evaporative stress acting on the cornea. We observed changes in corneal layer thicknesses and in scattering properties of the stroma, which are sensitive indicators of environmental stress leading to irritation of the ocular surface under dry eye conditions. The combination of corneal culture under desiccating conditions and OCT monitoring offers a new perspective in understanding and treating of DES and is expected to allow for significant pharmacological screening tests. Copyright © 2010 S. Karger AG, Basel.

Abstract: About those overlooked and underestimated lid margins

The Lid Margin Is an Underestimated Structure for Preservation of Ocular Surface Health and Development of Dry Eye Disease.

Dev Ophthalmol. 2010;45:108-122. Epub 2010 May 18.
Knop E, Korb DR, Blackie CA, Knop N.
Research Laboratory, Department of Ophthalmology CVK, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Purpose: The structure of the lid margin is insufficiently understood and defined, although it is of obvious importance in ocular surface integrity.

Methods: The structure and function of the different zones of the lid margin are explained with a focus on dry eye disease.

Results: The posterior lid margin, which is of particular significance for the integrity of the ocular surface, includes the meibomian glands that open within the cornified epidermis. Their obstructive dysfunction is a main cause of dry eye disease. The orifice is followed by the mucocutaneous junction, which extends from the abrupt termination of the epidermis to the crest of the inner lid border. The physiological vital stainable line of Marx represents its surface, and can be used e.g. as a diagnostic tool for the location and functionality of the meibomian gland orifices and lacrimal puncta. The marginal conjunctiva starts at the crest of the inner lid border and forms a thickened epithelial cushion. This is the point closest to the globe, and represents the zone that wipes the bulbar surface and distributes the thin preocular tear film. It is hence termed the 'lid wiper' and pathological alterations that result in a vital staining are a sensitive early indicator of dry eye disease.

Conclusions: The margin of the eyelid is an important but currently underestimated structure in the maintenance of the preocular tear film and of the utmost importance for the preservation of ocular surface integrity and in the development of dry eye disease. Copyright © 2010 S. Karger AG, Basel.

Abstract: Hyperosmolarity of the Tear Film in Dry Eye Syndrome

Hyperosmolarity of the Tear Film in Dry Eye Syndrome.
Dev Ophthalmol. 2010;45:129-138. Epub 2010 May 18.
Messmer EM, Bulgen M, Kampik A.
Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany.

Hyperosmolarity of the tear film is recognized as an important pathogenetic factor in dry eye syndrome (DES). Hyperosmolarity testing has been hampered in the past by difficulties in tear collection and analytic procedures that required laboratory facilities. The Tearlab(TM) Osmolarity System is a new user-friendly tool that only needs tiny volumes for analysis and determines hyperosmolarity semi-automatically. We measured tear film osmolarity with the Tearlab in 200 healthy individuals and patients with DES. Dry eye diagnosis was established when >/=3 of the following criteria were fulfilled:(1) Ocular Surface Disease Index > 15; (2) staining of the cornea in the typical interpalpebral area; (3) staining of the conjunctiva in the typical interpalpebral area; (4) tear film break-up time < 7 s; (5) Schirmer test < 7 mm in 5 min; (6) the presence of blepharitis or meibomitis. Tear film osmolarity, as measured by Tearlab, did not show any correlation with the 6 clinical signs of dry eye. Moreover, tearfilm osmolarity testing could not discriminate between patients with DES (308.9 +/- 14.0 mosm/l) and the control group (307.1 +/- 11.3 mosml/l). Tear film osmolarity did not correlate to artificial tear use. Technical problems with the Tearlab, reflex tearing, or the difficulty in establishing a dry eye diagnosis with the recommended tests may account for these results. Further investigations are necessary before recommending this tool for daily clinical practice. Copyright © 2010 S. Karger AG, Basel.

Abstract: Systane Ultra

I suspect the Systane product line has more published studies than any other over the counter tear.

Novel Ocular Lubricant Containing an Intelligent Delivery System: Details of Its Mechanism of Action.
Dev Ophthalmol. 2010;45:139-147. Epub 2010 May 18.
Springs C.
Department of Ophthalmology, Indiana University, Indianapolis, Ind., USA.

Objective: The purpose of this review is to outline the mechanism of action of a novel ocular lubricant incorporating hydroxypropyl-guar (HPG) and the demulcents polyethylene glycol 400 and propylene glycol.

Methods: The literature relating to the mechanism of action of Systane Ultra is presented. The literature search covered the period prior to June 2008. A manual search was also conducted based on citations in the published literature. Additional original reports were referenced if relevant to the subject matter of the review.

Results and Conclusion: The published literature supports the efficacy of an ocular lubricant containing HPG at reducing the signs and symptoms of dry eye through its multiphasic behavior and duration of action. This new formulation presents an additional benefit of a delivery system to further reduce the assimilation time of the product on-eye. Beneficial outcomes have been documented for tear film interaction, blur profile, viscoelasticity and tensile strength. Copyright © 2010 S. Karger AG, Basel.

Monday, June 14, 2010

Abstract: Dry eye disease as an inflammatory disorder

In another ten years when we look back on this decade, I wonder, will we see true medical advances or will we all scratch our heads and wonder whether everyone was just drinking too much Restasis koolaid.

Dry eye disease as an inflammatory disorder.
Ocul Immunol Inflamm. 2010 Jun;18(3):190-9.
Calonge M, Enríquez-de-Salamanca A, Diebold Y, González-García MJ, Reinoso R, Herreras JM, Corell A.
IOBA (Institute of Opthalmo-Biology), University of Valladolid, Valladolid, Spain.

Purpose: Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression.

Methods: A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED.

Results: New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs.

Conclusions: Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

Abstract: Diadenosine Polyphosphates in Tears of Sjogren Syndrome Patients.

Diadenosine Polyphosphates in Tears of Sjogren Syndrome Patients.
Invest Ophthalmol Vis Sci. 2010 May 19. [Epub ahead of print]
Carracedo G, Peral A, Pintor J.
Optica II ( optometria y vision), Escuela Universitaria de Optica (UCM), Madrid, Spain.

Purpose. To analyze the levels of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in tears of subjects with Sjögren Syndrome and to compare with a control group.

Methods. Twelve subjects, diagnosed with Sjögren Syndrome, and 20 healthy subjects such as control, were invited to participate in the present study. Schirmer strips were used to measure tear secretion (Schirmer I test) and to collect tears. Ap4A and Ap5A were measured by high pressure liquid chromatography (HPLC) and a Dry Eye Questionnaire (DEQ) was used to evaluated dry eye symptomatology.

Results. The mean concentrations of Ap4A and Ap5A in the Sjögren Syndrome group were 2.54 +/- 1.02 microM and 26.13 +/- 6.95 microM respectively. This group of patients was divided in two groups, four patients with normal tear production and eight patients with low tear production. Concentrations of Ap4A, and Ap5A, in patients with normal tear production (Schirmer test value of 12.3 +/- 1.2 mm), were 0.47 +/- 0.20 microM and 8.03 +/- 3.27 microM respectively. In the patients with low tear production (Schirmer test value of 1.0 +/- 0.3mm) the Ap4A and Ap5A concentrations were 4.09 +/- 1.36 microM and 39.51 +/- 8.46 microM, respectively. In the control group the Ap4A and Ap5A concentrations were 0.13 +/- 0.03 microM and 0.04 +/- 0.02 microM, respectively.

Conclusions. It is concluded that patients with Sjögren Syndrome have abnormally elevated concentrations of diadenosine polyphosphates indicating that these compounds could be used for the diagnosis of this pathology.

Abstract: The practical stuff gets short shrift

These authors looked for studies of 'assistive technology' (read, practical help!) for adults with RA. The only one they found that met the criteria still wasn't really good enough to rely on. It sounds like one of those EZDrop type things that you can put on a bottle to help you aim.

Such a frustrating irony in dry eye: Many of us benefit greatly from 'consumer devices' - as much or more than from drugs. Yet these are never studied properly, because there's (relatively speaking) no money in it.

Eur J Phys Rehabil Med. 2010 Jun;46(2):261-8.
The Cochrane review of assistive technology for rheumatoid arthritis.
Tuntland H, Kjeken I, Nordheim L, Falzon L, Jamtvedt G, Hagen K.
Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, USA.

AIM: The aim of this systematic review is to summarise the available evidence on the effectiveness of assistive technology for adults with rheumatoid arthritis in terms of improving functional ability and reducing pain, and to assess potential adverse effects related to device use.

METHODS: In this review, randomised controlled trials, clinical controlled trials, controlled before and after studies and interrupted time series available through systematic searches (electronic databases, grey literature, contact with authors, reference lists) up to October 2008 were included. Two reviewers independently selected trials for inclusion, assessed the validity of included trials, and extracted data. Investigators were contacted to obtain missing information.

RESULTS: Out of 7177 hits, 13 articles were reviewed in full text and only one trial was finally included (N.=29). The study was a randomised crossover trial, in which the use of an eye drop device was compared to a standard bottle in people with rheumatoid arthritis suffering from persistent dry eyes. The results show that the eye drop device improved application of eye drops and prevented adverse effects in terms of touching the eye with the bottle tip. The study was considered to have low quality of evidence.

CONCLUSION: Since only one trial met the inclusion criteria for this review, there is very limited evidence for the effect of assistive technology for adults with rheumatoid arthritis. There is an urgent need for high-quality research in this field, in order to reach sufficient evidence on the effectiveness of this commonly used intervention.

Abstract: Adenosine A2 receptor & bunny lacrimal glands

Adenosine A2 receptor presence and synergy with cholinergic stimulation in rabbit lacrimal gland.
Curr Eye Res. 2010 Jun;35(6):466-74.
Carlsson SK, Edman MC, Delbro D, Gierow JP.
School of Natural Sciences, Linnaeus University, Kalmar, Sweden.

PURPOSE: Secretion from the lacrimal gland is an important part of the well-being of the eye, and a central part in the search for treatment of dry eye syndrome. Adenosine has stimulatory effects on the lacrimal gland, and can potentiate the effect of the cholinergic agonist carbachol (Cch). The aim of the present study is to investigate the presence of the adenosine A(2) receptor subtypes A(2A) and A(2B) in the rabbit lacrimal gland, and to characterize their role in regulated acinar cell secretion.

METHODS: Expression of the receptors was investigated using reverse transcriptase-PCR (RT-PCR) and immunofluorescence, and secretion effects were studied using a secretion assay in isolated lacrimal gland acinar cells.

RESULTS: Presence of both receptors was detected by RT-PCR and immunofluorescence. The secretion assay revealed a minor effect of stimulation of the A(2) receptors, and a strong synergistic effect with the cholinergic agonist Cch. The synergistic effect was significantly reduced by the A(2B) antagonist PSB 1115, but not by the A(2A) antagonist SCH 58261, indicating that A(2B) is the receptor responsible for this potentiation.

CONCLUSIONS: The study reveals the presence of the adenosine A(2) receptor subtypes as well as a role for them in lacrimal gland secretion, and especially in the synergy with purinergic and cholinergic stimulation.

Abstract: We need quality-of-life measures for dry eye

Impact of dry eye disease and treatment on quality of life.
Curr Opin Ophthalmol. 2010 May 12. [Epub ahead of print]
Friedman NJ.
aStanford University School of Medicine, Stanford, USA bMid-Peninsula Ophthalmology Medical Group, Palo Alto, California, USA.

PURPOSE OF REVIEW: Recent increased awareness of dry eye disease (DED) by both clinicians and patients has been accompanied by improved recognition that it is a chronic disorder often requiring long-term management. DED, frequently associated with symptoms of discomfort and visual disturbance, also impairs quality of life (QoL), including aspects of physical, social, and psychological functioning. This review summarizes the available research on the impact of DED and its treatment on measures of QoL.

RECENT FINDINGS: A relative dearth of data supporting the effectiveness of DED treatments as assessed by QoL measures exists. Both cyclosporine ophthalmic emulsion 0.05% and hydroxypropyl cellulose ophthalmic inserts have been associated with improvements in Ocular Surface Disease Index scores, a disease-specific measure of QoL, and with enhancement of patients' ratings regarding their ability to perform activities of daily living.

SUMMARY: Because there is a lack of concordance between symptoms and diagnostic measures of DED, QoL measures provide clinicians a valuable tool for assessing the burden of disease as well as response to treatment. Such measures should be employed in clinical practice and in future trials of treatment modalities.

Abstract: Argon laser punctal stenosis

8 of 13 patients required two to six re-treatments? Pretty determined contact lens wearers ya got there, doc.

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: Upper vs. lower plugs (collagen only)

I would REALLY like to see this study replicated with 3-month or 6-month plugs. Personally I don't really have all that much faith in collagen plugs as a proxy for what longer term plugs will do, both from personal experience and patient reports.

Upper punctal occlusion versus lower punctal occlusion in dry eye.
Invest Ophthalmol Vis Sci. 2010 May 12. [Epub ahead of print]
Chen F, Wang J, Chen W, Shen M, Xu S, Lu F.
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, China.

Purpose: To compare the effect of upper punctal cclusion and that of lower punctal occlusion in dry eye patients.

Methods: Occlusion of one eye's upper punctum and the contralateral eye's lower punctum with collagen plugs was performed in 20 dry eye patients. The same procedure was done in 20 normal subjects. The upper and lower tear menisci were imaged simultaneously by real-time OCT before punctal occlusion and repeated on days 1, 4, 7 and 10 afterwards. The subjective symptom scoring, corneal fluorescein staining, Schirmer I test, and tear break-up time (TBUT) were also performed.

Results: In dry eye patients, occlusion of either punctum improved symptom scores, fluorescein staining scores, TBUT, and lower tear meniscus height (LTMH, P < 0.05); however Schirmer test scores and upper tear meniscus height (UTMH) did not change after occlusion(P > 0.05). There was no significant difference for any of these variables between upper punctum occluded eyes and lower punctum occluded eyes before or after occlusion (P > 0.05). In normal subjects, Schirmer test scores, TBUT, UTMH, and LTMH did not change over time (P > 0.05).

Conclusion: Punctal occlusion with collagen plugs in dry eye patients leads to the relief of subjective symptoms and the improvement of objective signs. The effectiveness of occluding upper or lower punctum is similar. The LTMH is a valid indicator for the success of the punctal occlusion.

Abstract: Are doctors 'following the rules' with dry eye care?

Telling us what we know and which needs to be addressed:

Dry eye care, on average, has plenty of room for improvement.

Documentation of conformance to preferred practice patterns in caring for patients with dry eye.
Arch Ophthalmol. 2010 May;128(5):619-23.
Lin IC, Gupta PK, Boehlke CS, Lee PP.
Departments of Ophthalmology, Duke University Eye Center, Durham, NC 27710, USA.

OBJECTIVE: To evaluate documentation of physician evaluations of patients with dry eye for the presence of key elements as defined in the American Academy of Ophthalmology Summary Benchmarks for Preferred Practice Patterns.

METHODS: One hundred thirty-one medical records of patients seen at the Duke Eye Center from January 1998 to July 2008 were reviewed relative to both the dry eye preferred practice patterns benchmarks for 1998 (all patients) and 2003 (for those seen between 2004 and 2008). Overall total score and subsection scores were calculated for all patients, as well as by specialty provider types and by type of medical record (electronic vs paper).

RESULTS: Of all records reviewed, 84.8% were for women and the mean (SD) age of all patients was 60.3 (20.8) years. On average, 66.4% of the initial history key elements, 77.3% of the initial physical examination key elements, 40.0% of care management key elements, and 67.9% of patient education key elements were documented. The physical examination scores were highest in the "other" subspecialty ophthalmologist group compared with the comprehensive ophthalmologist group (P = .03) and cornea specialists (P = .02). The physical examination scores were 87% in the electronic medical record and 75% in the standard paper medical record (P < .001) groups.

CONCLUSIONS: In an academic practice, the process of care delivery for dry eye does conform to the American Academy of Ophthalmology Preferred Practice Patterns in some areas; however, there is room for improvement especially in the areas of patient education and care management. Additional data are needed from other practice settings to further evaluate the quality of dry eye care.

Abstract: The daily ups & downs of dry eye

Seems like a no-brainer to those of us who have it but the implications of this study for dry eye research are important. It's also helpful for patients to keep in mind when they visit their doctors... schedule those appointments accordingly, when possible!

Diurnal variation of visual function and the signs and symptoms of dry eye.
Cornea. 2010 Jun;29(6):607-12.
Walker PM, Lane KJ, Ousler GW 3rd, Abelson MB.
Ora, Inc, Andover, MA, USA.

PURPOSE: Subjects with dry eye often complain of disturbances in visual function and worsening of symptoms in the evening. To clinically substantiate these reports of diurnal variations, the present study tested subjects with dry eye on a series of visual function and ocular physiology measures.

METHODS: Twenty-one subjects with dry eye were enrolled and underwent ophthalmic examinations, including best spectacle-corrected visual acuity, visual function decay as measured by the interblink interval visual acuity decay test without ocular anesthetic, reading rate test, slit-lamp biomicroscopy, and tear film breakup time. Keratitis, conjunctival redness, and corneal sensitivity were also assessed. Examinations occurred once during the morning and for a second time in the evening. Subjects also completed a modified version of the Ocular Surface Disease Index at both study visits.

RESULTS: Subjects with dry eye showed impaired visual function in the evening, as compared to that in the morning; they maintained their best spectacle-corrected visual acuity for a shorter time between blinks (P < 0.01) and had longer readings times (P < 0.05) in the evening as compared with that in the morning. These findings were qualified by Ocular Surface Disease Index results showing greater subjective visual impairment in the evening. Subjects also demonstrated a significant increase in keratitis and conjunctival redness from morning to evening testing. Less ocular discomfort was reported in the evening than in the morning; this effect significantly correlated with corneal sensitivity in the evening.

CONCLUSIONS: Subjects with dry eye experience significant diurnal variations of visual function and ocular surface physiology. These daily rhythms should be considered when designing clinical trials and when quantifying disease severity.

Industry news: Valeant buys Aton (aka Lacrisert company)

On May 27th, Valeant Pharmaceuticals completed the purchase of Aton Pharma. Aton had acquired Lacrisert from Merck and has breathed new life into Lacrisert.

Valeant Pharmaceuticals Completes Acquisition of Aton Pharma, Inc.

ALISO VIEJO, Calif., May 27, 2010 /PRNewswire via COMTEX/ --Valeant Pharmaceuticals International (NYSE: VRX) today announced that effective May 26, 2010, the company completed its acquisition of Aton Pharma, Inc., a specialty pharmaceutical company focused on ophthalmology and certain orphan drug indications, located in Lawrenceville, New Jersey.

Abstract: Tear lipocalin and lysozyme concentrations in postmenopausal women

Tear lipocalin and lysozyme concentrations in postmenopausal women.
Ophthalmic Physiol Opt. 2010 May;30(3):257-66.
Srinivasan S, Joyce E, Boone A, Simpson T, Jones L, Senchyna M.
Centre for Contact Lens Research, School of Optometry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.

PURPOSE: To investigate the potential relationship between subjective symptomatology, tear volume, and tear break up time with tear film lipocalin and lysozyme concentrations in a group of symptomatic dry-eyed postmenopausal (PM) women compared to age-matched controls.

METHODS: Eighty-five healthy PM females (>50 years of age) were categorized as mild or moderate dry eye (DE), or asymptomatic [non-dry eye (NDE)] based on their responses to the Ocular Surface Disease Index (OSDI) questionnaire. Non invasive tear breakup time (NITBUT) and tear secretion were measured. Tears were collected via capillary tube and an eye wash method. Tear lysozyme and lipocalin concentrations were determined via Western blotting.

RESULTS: Ocular Surface Disease Index responses revealed 16 mild DE, 30 moderate DE, and 39 NDE. The OSDI total score and sub scores for the DE groups were significantly greater than for the NDE group (p < 0.001). The mild and moderate DE groups exhibited significantly shorter NITBUTs compared to NDE (p < 0.004). Tear secretion using the Phenol Red Thread (PRT) test was found to be significantly lower in the moderate DE group compared to NDE (p < 0.001). No difference in tear lysozyme or lipocalin concentration was found between DE and NDE groups, irrespective of tear collection method, although method of collection significantly influenced absolute concentrations (p < 0.008). Significant correlations were not found between symptoms or signs of DE compared to either lipocalin or lysozyme concentration.

CONCLUSION: Within a PM population, lipocalin and lysozyme are invariant, irrespective of the presence and severity of DE symptoms. This is the first comprehensive study of lipocalin and lysozyme in dry-eyed PM women and our results suggest that neither protein would offer utility as a biomarker of DE.

Abstract: Hydrogel lens material characteristics associated with lens dehydration

Contact lens material characteristics associated with hydrogel lens dehydration.
Ophthalmic Physiol Opt. 2010 Mar;30(2):160-6.
Ramamoorthy P, Sinnott LT, Nichols JJ.
The Ohio State University, 320 West Tenth Avenue, Columbus, OH 43210, USA.

PURPOSE: To determine the association between material dehydration and hydrogel contact lens material characteristics, including water content and ionicity.

METHODS: Water content and refractive index data were derived from automated refractometry measurements of worn hydrogel contact lenses of 318 participants in the Contact Lens and Dry Eye Study (CLADES). Dehydration was determined in two ways; as the difference between nominal and measured (1) water content and (2) refractive index. Multiple regression models were used to examine the relation between dehydration and material characteristics, controlling for tear osmolality.

RESULTS: The overall measured and nominal water content values were 52.58 +/- 7.49% and 56.88 +/- 7.81% respectively, while the measured and nominal refractive indices were 1.429 +/- 0.015 and 1.410 +/- 0.017. High water content and ionic hydrogel lens materials were associated with greater dehydration (p < 0.0001 for both) than low water content and non-ionic materials. When dehydration was assessed as the difference in refractive index, only high water content was associated with dehydration (p < 0.0001).

CONCLUSIONS: High water content and ionic characteristics of hydrogel lens materials are associated with hydrogel lens dehydration, with the former being more strongly associated. Such dehydration changes could in turn lead to important clinical ramifications such as reduced oxygen transmissibility, greater lens adherence and reduced tear exchange.

Sunday, June 13, 2010

OTC drop news: Soothe Xtra Hydration launched

Bausch & Lomb has launched a new preserved over-the-counter drop called Soothe Xtra Hydration. The active ingredients are a very slightly reduced concentration of the same actives as the basic Soothe preservative-free drops. It is not yet listed in B&L's website, but it is in drugstores and online.

Here's a quick run-down of the active ingredients of all three products currently sold under the Soothe brand:

Soothe XP Emollient Eye Drops [preserved]: Light mineral oil (1%), mineral oil (4.5%)
(This is the original milky-looking Soothe that used to be sold in the purple and orange box before B&L bought it from Alimera. It was re-named Soothe XP after the acquisition.)

Soothe Lubricant Eye Drops [preservative-free]: Glycerin (0.6%), propylene glycol (0.6%)
(This was added to the lineup when the original Soothe became Soothe XP.)

Soothe Xtra Hydration [preserved]: Glycerin (0.55%), propylene glycol (0.55%)
(This is the one just announced.)

I guess I'd better put the press release here too. Takes some imagination to squeeze four paragraphs about a drop that's not new enough in concept to hazard listing the ingredients....

Marketwire, May 4
Bausch + Lomb Introduces New Soothe® Xtra Hydration Dry Eye Therapy Lubricant Eye Drops

MADISON, NJ--(Marketwire - May 4, 2010) - Bausch + Lomb today announced the U.S. launch of new Soothe® Xtra Hydration lubricant eye drops. Building on the success of the Soothe XP Xtra Protection formula, new Soothe Xtra Hydration provides a comprehensive over-the-counter portfolio for patients with dry eyes.
The Soothe portfolio is now aligned with the most recent international Dry Eye Workshop (DEWS) sponsored by the Tear Film & Ocular Surface Society. DEWS created a new definition of dry eye and helped develop two major classifications of dry eye -- aqueous-deficient dry eye and evaporative dry eye.
New Soothe Xtra Hydration, for aqueous-deficient dry eye therapy, moisturizes and restores the deficient aqueous and mucin layers of the tear film to provide lasting hydration and comfort. It will be available at major retailers in May.
Soothe XP Xtra Protection, for evaporative dry eye therapy, re-establishes the lipid layer of the tear film to provide up to eight hours of relief. The product is widely available at major retailers.

Abstract: Graves orbitopathy & the cornea

Corneal involvement in Graves' Orbitopathy: an in vivo confocal study.
Invest Ophthalmol Vis Sci. 2010 Apr 30. [Epub ahead of print]
Villani E, Viola F, Sala R, Salvi M, Mapelli C, Currò N, Vannucchi G, Beck-Peccoz P, Ratiglia R.
Università degli Studi di Milano, Milan, Italy.

Purpose: To study the clinical involvement of the ocular surface, and the in vivo morphology of corneal cells and nerves, in patients affected by active and inactive Graves' orbitopathy (GO).

Methods: The study included 26 consecutive GO patients and 20 age- and gender-matched healthy control subjects. GO was diagnosed on the basis of the criteria of the European Group On Graves' Orbitopathy, and disease activity was evaluated by the Clinical Activity Score (CAS). Each participant underwent a full eye examination including an evaluation of symptoms (Ocular Surface Disease Index score), tear break-up time, fluorescein and lissamine green staining, corneal apex sensitivity and Shirmer's test. The corneal apex was examined by means of confocal microscopy in order to investigate the number and morphology of epithelial and stromal corneal cells and sub-basal nerves.

Results: Eleven of the 26 patients (43%) had active GO. One-way ANOVA with least-significant difference (LSD) post hoc test revealed statistically significant differences between patients and controls in all of the evaluated parameters except corneal sensitivity and nerve reflectivity. Among the GO patients, the only significant difference observed in active compared to inactive disease was in the number of hyper-reflective (activated) keratocytes (P<0.001, LSD). Corneal sensitivity inversely correlated with proptosis (P<0.001, Spearman's test).

Conclusions: GO patients show clinical and confocal corneal alterations, and signs and symptoms partially related to dry eye disease. The ocular surface inflammation in GO seems to be due to both the dry eye and the autoimmune orbitopathy.

Drug news: SAR1118 Phase 2 results

SARcode Corporation Announces Phase 2 Study Results of SAR 1118 Topical Ophthalmic Solution for the Treatment of Dry Eye
PRNewswire, 5/3/2010

Study Shows Improvements in Both Signs and Symptoms of Disease
SAN FRANCISCO, May 3 /PRNewswire/ -- SARcode Corporation, a privately-held biotechnology company focused on developing a novel class of lymphocyte function-associated antigen-1 (LFA-1) antagonists, today announced results of a 230 patient Phase 2 proof-of-concept study evaluating topical SAR 1118 ophthalmic solution in the treatment of aqueous deficient dry eye (keratoconjunctivitis sicca). The study results were presented at the Dry Eye Summit meeting on April 30th in Fort Lauderdale, Florida, immediately prior to ARVO 2010, the annual meeting of the Association for Research in Vision and Ophthalmology. The study results demonstrated clear improvements in both signs and symptoms of dry eye at 12 weeks. SAR 1118 was well-tolerated, with no serious ocular adverse events reported.

"We are very pleased with the results of the Phase 2 study," said Charles Semba, MD, chief medical officer of SARcode. "We met our goals of showing improvements in both corneal staining and patient symptoms. We were encouraged too that SAR 1118 achieved these results within 12 weeks, suggesting that it might provide more rapid relief than currently available therapies."

About the Phase 2 Study

The study was a randomized, multicenter, double-masked study comparing SAR 1118 (0.1, 1.0, 5.0%) to placebo. A total of 230 subjects were randomized 1:1:1:1 to receive drops twice daily for 12 weeks. The primary objective measure was inferior corneal staining. The major secondary measures were Ocular Surface Disease Index (OSDI) symptom score and tear production by Schirmer tear test (STT)....

About SAR 1118

SAR 1118 is a potent novel small molecule lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; alpha L beta 2) antagonist that can be targeted against a broad range of ocular inflammatory conditions including dry eye, uveitis, and diabetic macular edema. LFA-1 is member of the integrin family of adhesion receptors found on the surface of all leukocytes and represents a therapeutic target of the immune system central to a number of inflammatory stimuli, whether mediated by cytokines, prostaglandins, leukotrienes or complement. SAR 1118 has demonstrated significant potency in in vitro models in inhibiting cell adhesion, cytokine production, and cellular proliferation.