Wednesday, April 21, 2010

Abstract: It's the preservative, stupid

Prevalence of Ocular Surface Complaints in Patients With Glaucoma Using Topical Intraocular Pressure-Lowering Medications.
Cornea. 2010 Apr 9. [Epub ahead of print]
Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC.
From the *Department of Ophthalmology, New Jersey Medical School, Newark, NJ; daggerGlaucoma Associates of Texas, Dallas, TX; double daggerBascom Palmer Eye Institute, University of Miami, Miami, FL; section signPRN Pharmaceutical Research Network, LLC, Dallas, TX; and paragraph signAlcon Laboratories, Inc, Fort Worth, TX.

PURPOSE:: To determine the prevalence of ocular surface disease (OSD) in patients with glaucoma using topical intraocular pressure (IOP) -lowering therapy.

METHODS:: This prospective observational study enrolled patients with primary open-angle glaucoma or ocular hypertension who were on a topical IOP-lowering medication regimen. Enrolled patients completed the ocular surface disease index (OSDI) and OSDI scores (0-100, with 0 representing no symptoms) were calculated for each patient. Medical history, demographics, and concomitant medication information were also collected.

RESULTS:: Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms. OSDI scores were significantly different between patients with and without a prior diagnosis of dry eye syndrome (25.2 +/- 15.4 vs 15.4 +/- 15.8, respectively; P = 0.0036) and between patients who did and did not use artificial tears at the time of study participation (23.0 +/- 15.6 vs 15.3 +/- 15.8, respectively; P = 0.0046). Mean OSDI scores varied significantly with the number of topical IOP-lowering medications used, with higher (more severe) OSDI scores in patients using multiple IOP-lowering medications. Specifically, patients on a single medication had a mean OSDI score of 12.9 +/- 13.1, which was significantly lower than those of patients on 2 (16.7 +/- 17.0; P = 0.007) or 3 medications (19.4 +/- 18.1; P = 0.0001).

CONCLUSIONS:: OSD is prevalent among medically treated patients with glaucoma. The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.

Abstract: Hyaluronic acid molecular weights

Comparative studies of various hyaluronic acids produced by microbial fermentation for potential topical ophthalmic applications.
J Biomed Mater Res A. 2010 Mar 15;92(4):1421-30.
Guillaumie F, Furrer P, Felt-Baeyens O, Fuhlendorff BL, Nymand S, Westh P, Gurny R, Schwach-Abdellaoui K.
Novozymes Biopolymer A/S, Krogshoejvej 36, DK-2880 Bagsvaerd, Denmark.

This work presents a comparative study of various hyaluronic acids (HA) produced by fermentation of either Bacillus subtilis or Streptococcus towards the selection of an optimal molecular weight (MW) HA for the preparation of topical ophthalmic formulations. The influence of HA MW on water binding capacity, sterile filtration, rheological properties, precorneal residence time and ocular tolerance of ophthalmic solutions was investigated. Molecular weight did not affect hydration of hyaluronic acid according to differential scanning calorimetry (DSC). In general, medium MW HA (0.6-1 MDa) resulted in solutions that were superior in terms of sterile filtration and kinematic viscosity requirements compared to high MW HA (>1 MDa). Moreover, all HA-based solutions exhibited well-defined viscoelastic properties that depend on MW. Gamma scintigraphic data indicated that HA MW at 0.1% concentration (w/v) and HA origin did not significantly affect the corneal residence time on rabbit eyes. A 0.3% solution of high MW HA had a prolonged residence time in the precorneal area compared to a medium MW HA at the same concentration. Finally, an in vivo ocular irritation test based on confocal laser scanning ophthalmoscopy (CLSO) conclusively showed the excellent tolerance of both Bacillus-derived HA and Streptococcus-derived HA after topical instillation onto the corneal surface. Overall, this comprehensive work highlights the superiority of medium MW hyaluronic acid for topical ophthalmic formulations based on their physico-chemical and biological properties, tolerance and handling. Such solutions are expected to enhance tear film stability, to allow for maximum comfort, and to exhibit high residence times, while being biocompatible and easy to sterile filter. (c) 2009 Wiley Periodicals, Inc.

Abstract: Yes, we already know older women get dry eye the most....

Tear film evaporation-Effect of age and gender.
Cont Lens Anterior Eye. 2010 Apr 8. [Epub ahead of print]
Guillon M, Maïssa C.
OTG Research & Consultancy, London, UK.

PURPOSE: Dry eye is more prevalent in older patients and among them more marked in women than men. The increase in dry eye with aging is traditionally thought to be associated with a decrease in tear production enhanced by hormonal changes. Clinical evidence of an abnormal lipid production system in older patients, in particular women is established. It is therefore postulated that the greater prevalence of dry eye problems in an older population has an evaporative component. METHODS: Tear film evaporation was measured with the Oregon Health Sciences University Evaporimeter at 30% and 40% humidity. RESULTS: 160 subjects less than 45 years old and 57 subjects aged 45 years or more formed the study population. The results revealed a significant effect of age (p < 0.001), gender (p < 0.001) and their interaction (p < 0.001): (i) the rate of evaporation was higher in the older age group at both humidities; (ii) the rate of evaporation was overall higher for women; and (iii) the synergic effect of age and gender was very marked: the rate of evaporation of older women was 34-80% higher than that of older men and 36-69% than younger women. CONCLUSIONS: Aging of the tear film includes a significant evaporative component characterised by higher tear film evaporation for the over 45 compared to younger people. Further, in the over 45 years of age, a significantly greater tear film evaporation was recorded in women than men. The findings have significant implications for the management of presbyopic dry eye sufferers. Copyright © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Newsblurb: Sleep apnea and floppy eyelid syndrome

Sleep Apnea Linked to Hard-to-Diagnose Eye Disorders

A British study finds that the condition known as floppy eyelid syndrome (FES) is strongly associated with obstructive sleep apnea (OSA), implying that when doctors see FES in a patient, they should also look for OSA, and vice-versa. The study, published in April's Ophthalmology, the journal of the American Academy of Ophthalmology, describes factors shared by OSA and FES and specific findings on how FES develops that will help doctors better diagnose and treat patients.
People with OSA face several health challenges -- at worst, they are at risk of dying of oxygen deprivation when breathing slows or stops during sleep. OSA can contribute to or be aggravated by high blood pressure, diabetes, obesity and other systemic problems. Researchers led by Daniel G. Ezra, MD, MRCOphth, of Moorfields Eye Hospital, London, England, found the strong OSA-FES association in a case-controlled study of 102 patients tracked between 1995 and 2008; 102 matched controls were also tracked.

"About one-third (32 of 102) FES patients in our study also had OSA," Dr. Ezra said. "The significant association of the two disorders was evident even when we considered and controlled for patients' body-mass index (BMI, an indicator of whether obesity was a factor). FES is often considered a disease of overweight, middle-aged men, but our study did not find a patient cluster based on age, gender or BMI," he added.

People with FES have rubbery-textured upper eyelids that may easily flip up during sleep, exposing the "whites of the eyes," which can lead to dry, irritated eyes and/or discharge. The Moorfields research and other studies suggest that central nervous system arousal may be impaired in OSA sufferers, so they do not wake up as people normally do when breathing slows or stops, or when the eyelid is subjected to extreme stress. People with OSA often preferentially sleep on one side, which could result in intense, repeated pressure on the eyelid on that side of the face. A combination of these factors may contribute to or cause FES. The Moorfield report notes that FES resolved in an OSA patient who was treated with a continuous positive airway pressure mask.

Also, the Moorfields study confirms earlier findings that FES is associated with keratoconus, in which the cornea thins out and becomes cone-shaped. Patients with FES often rub their eyes excessively, perhaps contributing to keratoconus. Eye M.D.s (ophthalmologists) should recognize that visual problems in patients with FES may be due to keratoconus -- rather than dry eye disease or other surface irritation -- and treat them accordingly, the researchers say.

In a separate study, Dr. Ezra and colleagues followed 78 FES patients who had had been treated surgically for FES at Moorfields Eye Hospital within a 13 year period that began in 1995. Of the surgical methods used, better outcomes resulted for the procedures known as medial and lateral canthal placation, and upper lid lateral tarsal strip. But outcomes for all procedures were less favorable than reported in earlier studies; the Moorfields study attributes this difference to their study's longer follow-up period.

Drop (?) news: New Alcon drop

According to an analyst report, apparently a new consumer formulation is to be filed with the FDA this year. Name, nature unknown at present.

Drop (?) news: Systane ORB on the way

Don't know what it is, but it's supposedly headed to market later this year.

Device news: Hydrodynamic cavitation....

No (cough) comment.

Comfort Zone Labs Introduces a New Therapeutic Device That Kisses Good-Bye Dry-Eye Syndrome

When a doctor examines a patient for dry eyes, it has been statistically tabulated that 70% of patients with dry eye symptoms have signs of meibomian gland diseases, for which finding relief is much more difficult.

Orange County, CA, April 03, 2010 --( Keep those eyes nice, clean and healthy: Get rid of and keep away nasty blepharitis (which you may have and not know it but whether you know it or not, dry eye or lid therapy with this newly invented therapeutic device producing radial motion of warm gentle bubble waves can help it); prevent infections; shoo away debris/offending objects and clean up insidious eyelid dandruff and experience true gentle prolonged relief.

Classical approach to this problem is to perform in-house surgical meibomian gland expression, using two cotton-tip applicators and applying manual pressure to the glands of the lower lids, expressing the opaque, inspissated, and staph-laden material. The hard part is performing it on the upper lid where the patient feels extraneous pain and discomfort. If you ever had this lipid catharsis performed, you already know from your own grotesque personal experience with the sheer amount of “gunk” extracted and pain that entails classical procedures and techniques doctors use today, since nothing else is available.

This patent pending therapeutic device is directed towards a new dry eye cleaning process without feeling pain. This therapeutic device has a sophisticated and advanced irrigation system employing hydrodynamic cavitation producing transient radial motion of bubbles wherein the individual manipulates the hand piece of the sealed eye cup irrigator to wash or remove gunk’s from his/her eyes. The irrigator nozzle is configured to produce transient radial motion of bubbles in the water stream. This hydrodynamic cavitation process produces a chemical breakdown product, which combat bacterium, while dislodging lipids or other offending foreign objects from the eyes. Thus this invented therapeutic device is directed towards a new principle of applying hydrodynamic cavitation process producing transient radial motion of bubble waves that simultaneously deposits produced radicals and ions to the eye surface, and is hereby designed by Comfort Zone Labs. Furthermore, this hydrodynamic therapeutic device system automatically flushes the unwanted infectious materials into an attached hazardous safety disposable bag while undergoing rapid fluidic exchanging process. The residual offending materials that are automatically flushed from the eye membrane can be disposed safely.

This therapeutic device help your tears, directly and indirectly-directly, by improving some of the really important stuff that goes into your tears and indirectly, by getting rid of or preventing nasty stuff that gets in the way and makes dry-eye conditions worse or creates conditions that feel like dry-eye.

Here is how it helps four ways that no other device in the market can perform.

1) It retains moisture while cleaning and after cleaning.
2) It acts as a powerful agitator while sanitizing with warm circulating transient radial motion of bubble waves to liquefy the toothpaste like secretion plugging the glands.
3) The intense vibrations mode produced by radial motion of bubble waves, closes the microvasculature that is feeding the inflammatory mediators to the glands that inhibit normal function.
4) The warm transient radial motion of bubble waves therapeutically improves lid opposition. Therefore, the pumping mechanism of the meibomian glands improves after this therapy with far greater instant results. Hence, recurrent blepharitis ends.

It is known that many treatments for the dry-eye only helps with medications. Hydrodynamic therapy immediately reliefs and improves symptoms and the meibomian glands functions in the long term that benefits patients, due to the value added process that retains moisture in the infected eye accordingly. Post therapy after using this new device helps patients sleep comfortably.

This patent pending device was invented by Mr. Anwar Haq of Comfort Zone Labs. CZL is offering this device for licensing or joint venture.

Abstract: Lacrisert study

Improved Signs, Symptoms, and Quality of Life Associated With Dry Eye Syndrome: Hydroxypropyl Cellulose Ophthalmic Insert Patient Registry.
Eye Contact Lens. 2010 Mar 26. [Epub ahead of print]
Koffler BH, McDonald M, Nelinson DS; for the LAC-07-01 Study Group.
From the Koffler Vision Group (B.H.K.), Lexington, KY; NYU School of Medicine (M.M.), New York, NY; and InterQuest Medical (D.S.N.), Mountain Lakes, NJ.

OBJECTIVES: To evaluate the acceptability, ease of use, and efficacy of hydroxypropyl cellulose ophthalmic inserts in reducing signs and symptoms of moderate-to-severe dry eye syndrome (DES), and improving quality of life (QoL) and activities of daily living (ADL).

METHODS: The multicenter, prospective, open-label, 4-week registry comprised 520 patients with bilateral DES and a history of artificial tear use, or a desire to use artificial tears within the previous week. Visit 1 encompassed a clinical evaluation and symptom and QoL questionnaires, including the Ocular Surface Disease Index. Patients were trained to use inserts, which were used once daily, thereafter, as monotherapy or with existing therapy. At visit 2, clinical evaluation and questionnaires evaluated changes in signs, symptoms, ADL, and QoL. Adverse events were monitored throughout the registry.

RESULTS: There were 418 (80.4%) completers. Statistically significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity, as well as clinical signs of keratitis, conjunctival staining, and tear volume were seen (P<0.05). Mean Ocular Surface Disease Index total scores improved by 21.3% (P<0.05). Blurred vision, affecting 8.7% of patients, was the most commonly reported adverse event leading to discontinuation.

CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly improved signs and symptoms of moderate-to-severe DES, as well as ADL and QoL. Benefits were additive to those seen with patients' existing care.

Abstract: More lid wiper epitheliopathy

Lid-Wiper Epitheliopathy in Contact Lens Users and Patients With Dry Eye.
Eye Contact Lens. 2010 Mar 26. [Epub ahead of print]
Yeniad B, Beginoglu M, Bilgin LK.
From the Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

OBJECTIVE: To evaluate lid-wiper epitheliopathy (LWE) in contact lens users and in patients with symptoms characteristic of dry eye but with normal dry-eye tests and to compare the results with those of controls.

METHODS: One hundred fifty-five patients were enrolled in the study and were divided into three groups. The first group included 69 contact lens users, the second group included 46 patients with dry eye, and the third group included 40 controls. The contact lens users were also divided as symptomatic and asymptomatic according to the Standard Patient Evaluation of Eye Dryness questionnaire and Ocular Surface Disease Index. The patients were examined for LWE with three different dyes (fluorescein, rose bengal, and lissamine green). The results were compared using chi-square and T tests.

RESULTS: More LWEs were detected in the contact lens and dry-eye groups compared with controls. In the contact lens group, 67% of the symptomatic patients and 32% of the asymptomatic patients showed LWE. The difference was statistically significant (P = 0.001). No significant correlation was found between LWE and the dry-eye tests (fluorescein breakup time and Schirmer test).

CONCLUSIONS: LWE should be investigated in symptomatic contact lens users and in patients with symptoms characteristic of dry eye but with normal dry-eye tests. Lid wiper may traumatize the corneal epithelium and increase the sensitivity of the cornea. This could be the main cause of the symptoms in patients without any significant dry-eye test findings.

Abstract: Contact lenses, computers, blinking, and the tear film

I really enjoyed this one... sounds like a well put together study. More details about what goes on with blinking when you have contacts in (or not) and are staring at a screen or thinking about something else.

Effect of Contact Lens Wear and a Near Task on Tear Film Break-Up.
Optom Vis Sci. 2010 Mar 25. [Epub ahead of print]
Jansen ME, Begley CG, Himebaugh NH, Port NL.
*OD, MS daggerOD, MS, FAAO double daggerOD, PhD section signPhD Indiana University School of Optometry, Bloomington, Indiana.

PURPOSE.: To study the effect of extrinsic controls on blinking by examining blink parameters and tear stability among adapted soft contact lens (CL) wearers performing tasks that require varying amounts of visual concentration.

METHODS.: The Demographic Questionnaire, Contact Lens Dry Eye Questionnaire, and Current Symptoms Questionnaire were completed by 15 adapted soft CL wearers (nine females). Three 55 s simultaneous measurements of tear film stability via retroillumination and blinking were obtained with a slit-lamp biomicroscope and 200 Hz video camera while subjects listened to music and played a video game with and without their habitual CLs. Interblink interval (IBI) and blink amplitude (BA) were calculated. The area of break-up (AB) was calculated for the retroillumination image before each blink. The Current Symptoms Questionnaire was completed four times throughout testing.

RESULTS.: With the game compared to music, IBI was significantly longer and BA significantly decreased without CLs (p< / = 0.001). With CLs, the IBI did not significantly change between tasks but the BA significantly decreased (p = 0.100). The AB significantly increased with CL and the game (paired t-test, p/= 0.5579, p< 0.0001) and several symptom measures (Spearman r>/= 0.6262, p< 0.0001). The AB was significantly correlated with symptom measures including bothersome discomfort for the game with and without CLs (Spearman r >/= 0.5064, p< 0.0001).

CONCLUSIONS.: During tasks requiring concentration, the IBI increased (blink rate decreased) and many blinks were incomplete without CLs. With CLs, tear film instability increased. Blinking frequency also increased, but it remained high when subjects played the game, and symptoms of ocular irritation increased. This suggests that wearing soft CLs, even when fully adapted, provides enough extrinsic ocular surface stimulation to override internal controls and affect blink parameters.

Abstract: VisMed

Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (vismed, rejena).
Am J Ophthalmol. 2010 Apr;149(4):594-601.
Vogel R, Crockett RS, Oden N, Laliberte TW, Molina L; Sodium Hyaluronate Ophthalmic Solution Study Group.
Rx Development Resources, LLC, Tampa, Florida, USA.

PURPOSE: To evaluate the efficacy and safety of 0.18% sodium hyaluronate ophthalmic solution (Rejena, Vismed) compared with its vehicle for the treatment of signs and symptoms of dry eye disease.

DESIGN: Randomized, placebo-controlled clinical trial. METHODS: A total of 444 subjects with dry eye disease were randomized 1:1 to active study drug (n = 221) or vehicle control (n = 223) in this multicenter, double-masked trial. Subjects instilled 1 to 2 drops, 3 to 6 times daily for 14 days, with evaluations at Days 7 and 14. The study's 2 primary efficacy endpoints were change from baseline at Day 7 in lissamine green staining scores (objective) and in global symptom frequency scores (subjective). Results were analyzed using Wilcoxon rank sum test and Student t test in the intent-to-treat (ITT) population with last observation carried forward (LOCF).

RESULTS: At Day 7, the differences between the active and vehicle groups in change from baseline for lissamine green staining score (P = .050, Wilcoxon; P = .029, t test) and global symptom frequency score (P = .050, Wilcoxon; P = .017, t test) were both statistically significant. There were no clinically relevant safety findings related to the use of Rejena.

CONCLUSIONS: This study demonstrated the clinical efficacy of Rejena in the treatment of dry eye disease in both a primary objective endpoint and a primary subjective endpoint when compared to its vehicle. The study results also supported the well-known safety profile of Rejena

Abstract: Spitting snakes

Golly. Guess my list of possible dry eye causes is incomplete after all. - If you've been fretting over what could possibly have caused your dry eyes, perhaps you should take a review of your leisure activities....

Venom ophthalmia caused by venoms of spitting elapid and other snakes: Report of nine cases with review of epidemiology, clinical features, pathophysiology and management.
Toxicon. 2010 Mar 21. [Epub ahead of print]
Chu ER, Weinstein SA, White J, Warrell DA.
Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.

Venom ophthalmia caused by venoms of spitting elapid and other snakes: report of nine cases with review of epidemiology, clinical features, pathophysiology and management. Chu, ER, Weinstein, SA, White, J and Warrell, DA. Toxicon XX:xxx-xxx. We present nine cases of ocular injury following instillation into the eye of snake venoms or toxins by spitting elapids and other snakes. The natural history of spitting elapids and the toxinology of their venoms are reviewed together with the medical effects and management of venom ophthalmia in humans and domestic animals including both direct and allergic effects of venoms. Although the clinical features and management of envenoming following bites by spitting elapids (genera Naja and Hemachatus) are well documented, these snakes are also capable of "spraying" venom towards the eyes of predators, a defensive strategy that causes painful and potentially blinding ocular envenoming (venom ophthalmia). Little attention has been given to the detailed clinical description, clinical evolution and efficacy of treatment of venom ophthalmia and no clear management guidelines have been formulated. Knowledge of the pathophysiology of ocular envenoming is based largely on animal studies and a limited body of clinical information. A few cases of ocular exposure to venoms from crotaline viperids have also been described. Venom ophthalmia often presents with pain, hyperemia, blepharitis, blepharospasm and corneal erosions. Delay or lack of treatment may result in corneal opacity, hypopyon and/or blindness. When venom is "spat" into the eye, cranial nerve VII may be affected by local spread of venom but systemic envenoming has not been documented in human patients. Management of venom ophthalmia consists of: 1) urgent decontamination by copious irrigation 2) analgesia by vasoconstrictors with weak mydriatic activity (e.g. epinephrine) and limited topical administration of local anesthetics (e.g. tetracaine) 3) exclusion of corneal abrasions by fluorescein staining with a slit lamp examination and application of prophylactic topical antibiotics 4) prevention of posterior synechiae, ciliary spasm and discomfort with topical cycloplegics and 5) antihistamines in case of allergic kerato-conjunctivitis. Topical or intravenous antivenom and topical corticosteroids are contraindicated. Clinical outcome of venom ophthalmia is largely dependent on prompt treatment and appropriate follow-up. Copyright © 2010 Elsevier Ltd. All rights reserved.

Abstract: Acupuncture and dry eye

Literature review. Most significant finding is how little this has been studied. But also, half the studies found that acupuncture worked better than artificial tears.

Acupuncture for treating dry eye: a systematic review.
Acta Ophthalmol. 2010 Mar 16. [Epub ahead of print]
Lee MS, Shin BC, Choi TY, Ernst E.
Division of Standard Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.

Purpose: The objective of this review was to assess the effectiveness of acupuncture as a treatment option for treating the condition of dry eye.

Methods: We searched the literature using 14 databases from their inceptions to 3 December 2009, without language restrictions. We included randomized clinical trials (RCTs) comparing acupuncture with conventional treatment. Their risk of bias was assessed using Cochrane criteria.

Results: Six RCTs met all the inclusion criteria. Three RCTs compared the effects of acupuncture with artificial tears in patients with xerophthalmia or Sjögren syndrome. A meta-analysis of these data showed that acupuncture improved tear break-up times (p < 0.0001), Schirmer test scores (p < 0.00001), response rates (p = 0.002) and the region of cornea fluorescent staining (p = 0.0001) significantly more than artificial tears did. The other three RCTs compared the effects of acupuncture plus artificial tears with artificial tears alone. Two of these studies failed to show significant effects of acupuncture, while one reported significant effects. For Schirmer test scores and frequency of artificial tear usage, two RCTs reported superior effects of acupuncture plus artificial tears, while one RCT failed to do so.

Conclusion: These results provide limited evidence for the effectiveness of acupuncture for treating dry eye. However, the total number of RCTs, the total sample size and the methodological quality were too low to draw firm conclusions.

Drug news: EGP-467 expected to commence Phase III

In a news report on the results from the anterior uveitis study of this drug, they mentioned that it's expected to enter Phase III for the dry eye indication this quarter. (Phase II was completed last spring and this is the first news since that time.)

EyeGate Pharma Completes Phase II Study of EGP-437 in Patients With Anterior Uveitis

...In the second quarter of 2010, the Company plans to initiate a multi-center Phase III study in dry eye patients....

Abstract: Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye

Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye.
Ann Anat. 2010 Apr 20;192(2):65-9. Epub 2010 Feb 20.
Jäger K, Garreis F, Posa A, Dunse M, Paulsen FP.
Department of Anatomy and Cell Biology, Martin Luther University of Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale, Germany.

The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as beta-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye. High concentrations of L-arginine and L-lysine are necessary for the expression of beta-defensins. These are supplied by epithelial cells in inflammatory processes. The limiting factor for initiation of beta-defensin production is the transport of L-arginine and L-lysine into the cell. This transport is performed to 80% by only one transporter system in the human, the y(+)-transporter. This group of proteins exclusively transports the cationic amino acids L-arginine, L-lysine and L-ornithine and is also known under the term cationic amino acid transporter proteins (CAT-proteins). Various infections associated with L-arginine deficiency (for example psoriasis, keratoconjuctivitis sicca) are also associated with an increase in beta-defensin production. For the first time, preliminary work has shown the expression of human CATs in ocular surface epithelia and tissues of the lacrimal apparatus indicating their relevance for diseases of the ocular surface. In this review, we summarize current knowledge on the human CATs that appear to be integrated in causal regulation cascades of beta-defensins, thereby offering novel concepts for therapeutic perspectives. Copyright 2010 Elsevier GmbH. All rights reserved.

Abstract: AVR Lid cleanser results

I am not sure whether this is referring to Sterilid or another product under development. I will update this post when I hear back from AVR.

Time-Kill Assay Results for a Linalool-Hinokitiol-Based Eyelid Cleanser for Lid Hygiene.
Cornea. 2010 Mar 18. [Epub ahead of print]
Gilbard JP, Douyon Y, Huson RB.
Jeffrey P. Gilbard, MD February 19, 1954 - August 12, 2009 Dr. Gilbard was best known for his pioneering research that led to treatments for dry eye disease. He also was considered one of the first ophthalmologists and researchers to understand the correlation between nutrition and health of the eye. He was my friend and mentor in the field of ophthalmology. Robert Huson, Advanced Vision Research. From the *Department of Ophthalmology, Harvard Medical School, Boston, MA; and daggerAdvanced Vision Research, Woburn, MA.

PURPOSE:: Time-kill testing was performed for a linalool-hinokitiol-based eyelid cleanser against Pseudomonas aeruginosa, Moraxella catarrhalis, Escherichia coli, Serratia marcescens, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, and Pityrosporum ovale to evaluate its efficacy.

METHODS:: An inoculum of 1 mL of each test organism culture was added to 49 mL of test cleanser. At 30 seconds and 1 minute, 1 mL of sample was removed from each test mixture and added to 9 mL of neutralizer. Five milliliters of aliquots were incubated for 48 hour and counted for colony-forming units. Ten percent povidone-iodine was used as a control.

RESULTS:: At 30 seconds, the linalool-hinokitiol-based eyelid cleanser produced a 99.9999% reduction in P. aeruginosa, a 99.999% reduction in E. coli, a 99.99% reduction in M. catarrhalis and S. marcescens, a 99.9% reduction in MRSA, a 99.2% reduction in S. epidermidis, and a 97.5% reduction in S. aureus. At 1 minute, this cleanser achieved a95.8% reduction in P. ovale. At 30 seconds, povidone-iodine produced a 99.9999% reduction in P. aeruginosa and M. catarrhalis, a 99.999% reduction in S. marcescens and a 94.9% reduction in S. epidermidis. At 1 minute, 10% povidone-iodine produced a 93.8% reduction in E coli but failed to produce a 1-log reduction in S. aureus or MRSA.

CONCLUSIONS:: This linalool-hinokitiol-based eyelid cleanser may be helpful in the outpatient setting for patients with presurgical, blepharitis, punctal plug and dry eye, and in the inpatient setting for patients who are allergic to iodine, or as an adjunct to povidone-iodine.

New drug news: CF101

A study was published recently with details from the Phase II trial whose results were announced about this time last year:

Treatment of Dry Eye Syndrome with Orally Administered CF101 Data from a Phase 2 Clinical Trial.
Ophthalmology. 2010 Mar 19. [Epub ahead of print]
Avni I, Garzozi HJ, Barequet IS, Segev F, Varssano D, Sartani G, Chetrit N, Bakshi E, Zadok D, Tomkins O, Litvin G, Jacobson KA, Fishman S, Harpaz Z, Farbstein M, Yehuda SB, Silverman MH, Kerns WD, Bristol DR, Cohn I, Fishman P.
Assaf Harofe Medical Center, Zeriffin, Beer Yaakov, Israel.

OBJECTIVE: To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN: Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study.

PARTICIPANTS: Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group.

INTERVENTION: Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation.

MAIN OUTCOME MEASURES: An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events.

RESULTS: A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group.

CONCLUSIONS: CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Abstract: Treating glaucoma in dry eye patients

Brief abstract highlighting need for carefully considering the ocular surface when treating glaucoma patients. Author #2 is one of the top ocular surface experts worldwide.

[Treatment of glaucoma in patients with dry eye syndrome]
J Fr Ophtalmol. 2010 Apr;33(4):285-90. Epub 2010 Mar 20.
[Article in French]
Labbé A, Baudouin C.
Service d'ophtalmologie 3, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France.

The treatments of glaucoma or ocular hypertension are associated with numerous ocular surface changes. Similarly, these ocular surface modifications directly impact the effectiveness of these therapies. The management of patients with glaucoma or ocular hypertension also suffering from dry eye syndrome needs to reduce eye drop-induced toxicity as well as a specific treatment for the ocular surface

Abstract: Factors in stability of autologous serum eyedrops

This is an important study on serum drops which you should definitely take note of if you are using them or considering using them (or even had an unsuccessful attempt at using them). Or if you are a doctor employing this treatment or considering it. It was published last year and although I knew it was coming out, I still managed to miss it (sorry about that).

Based on what I hear from patients there is unfortunately very little standardization in the storage of serum eyedrops.

If you are using serum drops and they are being given to you in vials which are each meant to be used for days or weeks at a time, or if you are not keeping your drops frozen until use and the active vial refrigerated until used up, I strongly encourage you to read this abstract (conclusions at least), take it to your doctor and as if s/he has read the study.

Cornea. 2009 Feb;28(2):200-5.
Time- and temperature-dependent stability of growth factor peptides in human autologous serum eye drops.
Bradley JC, Simoni J, Bradley RH, McCartney DL, Brown SM.
Department of Ophthalmology and Visual Sciences, University of California at Davis, Sacramento, CA, USA.

PURPOSES: To develop a step-by-step production method for human autologous serum (AS) eye drops that was broadly compliant with US Food and Drug Administration requirements for reinjection of processed biological substances. To determine optimum storage conditions for AS eye drops by measuring the concentration of growth factor peptides (GFP) as a function of storage temperature and storage duration.

METHODS: AS derived from the blood of 3 healthy male volunteers was produced using a closed, vacuum-driven, cascade-filtration system under sterile, low-pyrogen conditions. In-process controls included methods for monitoring protein electrophoretic mobility and degradation rate and the content of free hemoglobin and endotoxin. Stability of transforming growth factor beta1, substance P, nerve growth factor, calcitonin gene-related peptide, insulin-like growth factor 1, and epidermal growth factor was evaluated at -15 degrees C, +4 degrees C, +25 degrees C, +37 degrees C, and +42 degrees C at different time intervals (hours to weeks). The main outcome measures were the concentrations of GFP, endotoxin, and lipid peroxidation by-products (a proxy measure for protein degradation) in dilute AS.

RESULTS: The stability of GFP varies: transforming growth factor beta1, nerve growth factor, epidermal growth factor, and insulin-like growth factor 1 were more temperature and time resistant, but substance P and calcitonin gene-related peptide significantly degraded at +4 degrees C in 24 hours. Endotoxin and lipid peroxidation by-products were not significantly increased by processing.

CONCLUSIONS: This pilot study developed a closed, cascade-filtration system that was an effective method for the production of high-quality, low-pyrogen AS. The processing method broadly complied with Food and Drug Administration requirements for reinjection of biological substances. Variable GFP stability was observed at +4 degrees C and above. For clinical use, AS should be packaged in daily-use containers, which should be stored frozen; the container in active use should be refrigerated between doses.

This study won an award for best cornea research with a first author under 40 years old.