The Dry Eye Digest - Dry eye blog

Abstract: VisMed vs Optive

2012-02-01T23:52:00.000-08:00

Patients apparently did no worse on Optive than in Vismed.

Randomized, phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease.

Purpose.
To compare a treatment containing carboxymethylcellulose (CMC) and the osmoprotective (OsPr) compatible osmolytes erythritol, L-carnitine, and glycerin (OsPr-CMC) with a standard sodium hyaluronate (Na-HY) formulation in patients with dry eye disease.

Methods.
This was a 3-month, phase III, noninferiority study. Patients were randomized 1:1 to receive OsPr-CMC (OPTIVE®) or Na-HY (VISMED®). The primary efficacy outcome was the mean change from baseline in total ocular staining at day 35, scored using the 15-point Oxford scale. Noninferiority was assessed using the adjusted means. The secondary efficacy outcome was change in ocular surface disease index (OSDI) score from baseline to day 35. Other outcomes included tear osmolarity, Schirmer-I test score, OSDI, ease of use, patient acceptability, tolerability, and safety.

Results.
A total of 82 patients were randomized. The primary efficacy analysis was per protocol (OsPr-CMC, n=37; Na-HY, n=29). OsPr-CMC was noninferior to Na-HY in terms of adjusted mean change (SE) in ocular staining score at day 35: -2.0 (0.33) with OsPr-CMC vs -1.7 (0.37) with Na-HY. Similar improvements were seen in tear osmolarity, Schirmer-I test score, OSDI, and ocular staining for OsPr-CMC and Na-HY. More patients treated with OsPr-CMC vs Na-HY liked using their eyedrops, reported that their eyes felt comfortable, and found the treatment easy to use. Both treatments were well tolerated, with no serious treatment-related adverse events.

Conclusions.
Compared with Na-HY, OsPr-CMC was noninferior in terms of efficacy and safety, preferred by patients, and easier to use. Osmoprotection using OsPr-CMC therefore represents a viable option for dry eye disease management.

Eur J Ophthalmol. 2012 Jan 27:0. doi: 10.5301/ejo.5000117. [Epub ahead of print]
Baudouin C, Cochener B, Pisella PJ, Girard B, Pouliquen P, Cooper H, Creuzot-Garcher C.
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris - France; Institut de la Vision, UMRS 968, UPMC, Paris - France.

Drug news: Seikagaku SI-614

2012-01-30T08:22:00.000-08:00

Hyaluronate drop starting Phase II in the US.

Seikagaku Initiates a Phase II Clinical Trial in the United States for SI-614, Indicated for Treatment of Dry Eye

Tokyo, Japan, January, 2012—Seikagaku Corporation (hereafter “Seikagaku”) (head office: Chiyoda-ku, Tokyo) hereby announces that SI-614 has entered into a Phase II clinical trial in the United States (U.S.) for the treatment of dry eye....

SI-614 is a modified hyaluronate with an excellent tear film stabilizing effect that is produced by Seikagaku’s proprietary technology. Ocular instillation of SI-614 is expected to improve the tear film instability of the three layers (lipid layer, aqueous layer, and mucin layer) and accompanied symptoms found in dry eye patients....

Abstract: Blephagel

2012-01-30T08:08:00.000-08:00

From what I've read of user comments on DryEyeTalk, patient acceptance of this product varies as much as it does with any of the others (Ocusoft, Sterilid and so on).

Tolerability and acceptability of Blephagel: a novel eyelid hygiene aqueous gel.

Commonly associated with dry eye, blepharitis is the most commonly encountered disorder in general ophthalmologic practice. Although anti-infective and anti-inflammatory therapies are available, eyelid hygiene is the cornerstone of effective management. A variety of products have been used to assist and encourage eyelid cleansing and massage. The present study examines the ocular and periocular tolerability and acceptability of Blephagel, a cosmetic, poloxamer-containing gel designed specifically for cleansing the eyelid in subjects with sensitive skin or eyes or contact lens users. Subjects with blepharitis and sensitive skin or eyes, a history of atopy, or who use contact lenses applied Blephagel twice daily at home. Clinical ophthalmologic examinations were conducted before and 21 days after aqueous gel application, and subjects completed a questionnaire on the acceptability of the preparation. Thirty-three predominantly female subjects entered and completed the study. A total of 36% of the subjects had used similar products in the past, 21% regularly. Upon questioning by the ophthalmologist, 85% of the subjects reported acceptability of the preparation as good to very good, and 73% rated the efficacy as good to very good. There were minor but statistically non-significant changes in fluorescein tear breakup time and visual acuity before and after 21 days of aqueous gel application. The questionnaire results indicated that the subjects found the product to be effective for cleansing the eyelids of mucus and squama around eyelash roots. Moreover, cosmetic qualities, sensation in use, and acceptability were also appreciated. No subject reported any adverse event considered to be related to the aqueous gel. Although the safety of Blephagel has already been established in standard tests, the current results suggest that it is also pleasant to use and acceptable to blepharitis patients with sensitive skin as an aid to an eyelid hygiene regime.

Clin Ophthalmol. 2012;6:71-7. Epub 2012 Jan 11.
Doan S.
Department of Ophthalmology, Bichat Hospital and Foundation, Paris, France.

Abstract: Pediatric ocular rosacea

2012-01-30T08:00:00.001-08:00

GREAT reminder not to miss this possible diagnosis even in kids!

Pediatric ocular rosacea: 2 cases.

Purpose.
To report the clinical course of 2 pediatric ocular rosacea cases with a significant delay until diagnosis.

Methods.
We report 2 interventional case reports. Case 1 is a 10-year-old boy with 2 years of recurrent bilateral blepharitis, repetition chalazion, conjunctival hyperemia, and corneal ulcers, without response to topical antibiotics or topical and systemic steroids. Case 2 is a 9-year-old girl with keratoconjunctivitis and repetition chalazion since she was 2 years old, without improvement after consulting several ophthalmologists and performing several treatments throughout those years.

Results.
Rapid response to systemic erythromycin with marked improvement of both cases within a few weeks.

Conclusions.
Ocular rosacea is frequently misdiagnosed, particularly in the pediatric population. To our knowledge, this report demonstrates a case with the longest history before diagnosis (7 years) and another case in which a conjunctival biopsy was performed.

Eur J Ophthalmol. 2012 Jan 3:0. doi: 10.5301/ejo.5000103. [Epub ahead of print]
Miguel AI, Salgado MB, Lisboa MS, Henriques F, Paiva MC, Castela GP.
Department of Ophthalmology, Centro Hospitalar de Coimbra, Coimbra - Portugal.

Abstract: Meibum expressibility scale

2012-01-18T23:37:00.000-08:00

The last study I'm going to look at tonight... how nice that it's actually something that I'm interested in.

Wouldn't it be nice if doctors would standardize on something like this? Sounds like they need a fair amount more work on it first. Besides which, we still need to get to a point when more doctors know enough about meibomian glands to realize they need to examine them in the first place!

Development of the 4-3-2-1 Meibum Expressibility Scale.

OBJECTIVES:
With increased interest in the assessment of meibomian gland dysfunction and evaporative dry eye, there remains a deficit in simple, clinically applicable grading scales for gland expression. A new scale to assess meibum expressibility is described.

METHODS:
A meibum expressibility scale was developed using a new standardized meibomian gland expression device, which provides constant pressure along the inferior lid. For the scale development, 30 patients (53.0±8.49 years; 93.33% female) with mild-to-moderate dry eye were compared with 13 normal, non-dry eye subjects (25.6±4.3 years; 46.1% female) using the meibum expression device developed by Korb and Blackie. The device was placed 4 glands lateral to the inferior punctum and 1 mm below the lash line and was held stable for 15 sec. The glands expressing meibum were counted. The weighted κ statistic was used to evaluate the extent of agreement, and a receiver operating characteristic curve was created to test the proposed scale.

RESULTS:
The mean number of glands that expressed from the worse lid in the normal group was 3.54±1.61, whereas 1.53±1.28 glands expressed in the dry eye group. In the dry eye group, 1 subject showed 5 glands expressing, and 29 demonstrated scores of 4 or less. In the normal group, 3 or more glands were expressible in 11 of 13 subjects.

CONCLUSIONS:
A 4-3-2-1 scoring system is proposed, whereby 4 or greater=normal expressibility, 3=mildly reduced expressibility, 2=moderately reduced expressibility, and 1 or lesser=severely reduced expressibility. Further validation of the scale is warranted.

Eye Contact Lens. 2012 Jan 13. [Epub ahead of print]
Meadows JF, Ramamoorthy P, Nichols JJ, Nichols KK.
From the College of Optometry, The Ohio State University (J.F.M., P.R.); and College of Optometry, University of Houston (J.J.N., K.K.N.).

Abstract: Relationship between upper & lower lid MGs

2012-01-18T23:29:00.000-08:00

Interesting one....

Relation Between Upper and Lower Lids' Meibomian Gland Morphology, Tear Film, and Dry Eye.

PURPOSE.:
To analyze relations between upper lid (UL) and lower lid (LL) meibomian gland (MG) morphology and tear film and the MG criteria ability to predict dry eye.

METHODS.:
MG, lipid layer, and non-invasive break-up time (NIBUT) were evaluated of the OD of 20 randomly selected subjects (female = 10; median age = 44.5 years, interquartiles = 39.5 to 55 years). Subjects were grouped into nine Ocular Surface Disease Index (OSDI)- and 11 OSDI+ by the OSDI. Non-contact infrared meibography and image analysis were performed to evaluate MG loss, MG thickness, and MG bent angle.

RESULTS.:
MG loss (Pearson correlation; r = 0.647, p = 0.003) and MG bent angle (r = 0.489, p = 0.027) were significantly correlated between lids, but MG thickness was not (r = -0.059, p = 0.413). MG loss was significantly (t-test; p = 0.048) less in the UL (median = 26.9%; LL = 32.3%), thicker in the LL (p < 0.001) and were more bent in the LL (p = 0.001). MG loss was significantly correlated to lipid-layer thickness (r < -0.597, p < 0.003) and NIBUT (r < -0.453, p < 0.030), whereas MG thickness and bent angle of the UL only were related to NIBUT (r < -0.563, p < 0.018). Combining MG loss of both lids (linear regression analysis) resulted in the best predictive ability of OSDI± (area under the receiver operative characteristic curve = 0.929, p = 0.001).

CONCLUSIONS.:
MG scores between lids were significantly different but correlated. MG loss was significantly correlated to tear film characteristics including lipid layer thickness and stability. MG thickness and bent angle of the UL were related to NIBUT. The combination of both lids' MG loss showed best predictive ability of dry eye.

Optom Vis Sci. 2012 Jan 12. [Epub ahead of print]
Pult H, Riede-Pult BH, Nichols JJ.

Abstract: Lipiflow versus WHAT?

2012-01-18T23:17:00.000-08:00

ARGHHH!

I want so much to see studies on Lipiflow, and here's one, but what does it do? Tells me that Lipiflow beats iHeat! You have GOT to be kidding me. Anything beats iHeat, whether it's the hated washcloth, or the hot potato or boiled eggs I hear some patients saying their doctors recommended, or just me holding my coffee cup against my eyelids... to say nothing of my beloved rice baggies or Thermoeyes or the myriad warm compresses sold commercially which, unlike iHeat, actually stand a chance of producing heat sufficient to liquefy meibum. No offense to the manufacturers but, er, when I tested it, iHeat was about as low on the warm compress totem pole as you can go.

I literally cannot conceive of a less useful warm compress treatment to compare Lipiflow efficacy to. Next please!

A New System, the LipiFlow, for the Treatment of Meibomian Gland Dysfunction (MGD).

PURPOSE:
To evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD).

METHODS:
This was a non-significant risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine subjects were randomized between LipiFlow (n=69) and WC control (n=70). Subjects in the LipiFlow group received a 12-minute LipiFlow treatment and were reexamined at 1 day, 2 weeks and 4 weeks. Control subjects received a 5-minute iHeat treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, they crossed over (LipiFlow Crossover) and received the LipiFlow treatment. Effectiveness parameters: meibomian gland (MG) assessment, tear break-up time (TBUT) and dry eye symptoms. Safety parameters: adverse events, ocular health exam, ocular surface staining, intraocular pressure, visual acuity and discomfort.

RESULTS:
LipiFlow resulted in significant improvement (P < 0.05) in MG secretion at 2 and 4 weeks (mean ± standard deviation at baseline = 6.3 ± 3.5; 2 weeks = 14.3 ± 8.7; 4 weeks = 16.7 ± 8.7); and TBUT at 2 and 4 weeks: (at baseline = 5.5 ± 2.9; 2 weeks = 6.9 ± 5.0; 4 weeks = 7.4 ± 5.5). There was no significant change in MG secretion or TBUT in the control group. LipiFlow resulted in a greater significant reduction in dry eye symptoms than the iHeat WC. The crossover group demonstrated similar significant improvement 2 weeks post-treatment with the LipiFlow. There was no significant difference between groups in the incidence of non-serious, device-related adverse events.

CONCLUSION:
The LipiFlow System was significantly more effective than iHeat WC. These results support its safety and effectiveness in the treatment of MGD and dry eye symptoms.

Cornea. 2012 Jan 4. [Epub ahead of print]
Lane SS, Dubiner HB, Epstein RJ, Ernest PH, Greiner JV, Hardten DR, Holland EJ, Lemp MA, McDonald JE 2nd, Silbert DI, Blackie CA, Stevens CA, Bedi R.

Abstract: MG expression - How hard to press, and how bad does it hurt?

2012-01-18T23:07:00.000-08:00

Answers: Very hard. Very bad.

This is about the 35th abstract I've gone through tonight and it was so nice to finally come across something I could chew on. Gotta love that Dr. Korb. It's just plain guaranteed to be interesting and informative. I don't always like the answers (this study being one of them!) but it sure is interesting. Bottom line of his work here is, less than 1 in 10 people can tolerate the pain from a "therapeutic meibomian gland expression". Count me out :)

Meibomian gland therapeutic expression: quantifying the applied pressure and the limitation of resulting pain.

OBJECTIVES:
The purposes of this study were to determine (1) the pressure required to express the first nonliquid material from nonfunctional lower lid meibomian glands, (2) the pressure required to evacuate all of the expressible material from the glands (simulating the authors' methodology for therapeutic meibomian gland expression), and (3) the level of pain associated with these procedures.

METHODS:
All patients (n=28) were recruited from those presenting for ocular examinations at a single practice. Custom instrumentation exerting pressures from 1.0 to 150.0 psi was developed to quantify the pressure applied during expression. The instrument was applied to the inner surface of the lower lid. The lid was then compressed between the thumb and the contact surface of the instrument. The applied pressure was displayed on a digital meter. The first procedure evaluated the pressure required to obtain the first nonliquid material from nonfunctional glands. The second evaluated the pressure required for evacuating all expressible gland contents. The pain response was monitored throughout the procedure.

RESULTS:
The pressure to obtain the first nonliquid material ranged from 5 to 40 psi (mean=16.1±8.2 psi) and for the evacuation of expressible contents, from 10 to 40 psi (mean=25.6±11.4 psi). Only 7% of the patients could tolerate the pressure necessary to administer complete therapeutic expression along the entire lower eyelid.

CONCLUSIONS:
Forces of significant magnitude are required for therapeutic expression. Pain is the limiting factor for the conduct of this treatment.

Eye Contact Lens. 2011 Sep;37(5):298-301.
Korb DR, Blackie CA.
Korb Associates, Boston, MA, USA.

Abstract: Air pollution role in worsening blepharitis

2012-01-18T22:53:00.000-08:00

Ambient levels of air pollution induce clinical worsening of blepharitis.

Background:
Even though air pollutants exposure is associated with changes in the ocular surface and tear film, its relationship to the clinical course of blepharitis, a common eyelid disease, had not yet been investigated. Our objective was to investigate the correlation between air pollution and acute manifestations of blepharitis.

Method:
We recorded all cases of changes in the eyelids and ocular surface, and rated clinical findings on a scale from zero (normal) to two (severe alterations). Daily values of carbon monoxide, particulate matter smaller than 10μm in diameter and nitrogen dioxide concentrations and meteorological variables (temperature and relative humidity) in the vicinity of the medical service were obtained. Specific linear regression models for each outcome were constructed including pollutants as independent variables (single pollutant models). Temperature and humidity were included as confounding variables.

Results:
increases of 28.8μg/m(3) in the concentration of particulate matter and 1.1ppm in the concentration of CO were associated with increases in cases of blepharitis on the day of exposure (5 cases, 95% CI: 1-10 and 6 cases, 95% CI: 1-12, respectively).

Conclusion:
Exposure to usual air pollutants concentrations present in large cities affects, in a consistent manner, the eyes of residents contributing to the increasing incidence of diseases of the eyelid margin.

Environ Res. 2011 Dec 26. [Epub ahead of print]
Malerbi FK, Martins LC, Saldiva PH, Braga AL.
Department of Ophthalmology, Hospital Israelita Albert Einstein, São Paulo, Brazil; Environmental Epidemiology Study Group, Laboratory of Experimental Air Pollution, University of São Paulo Faculty of Medical Sciences, São Paulo, Brazil.

Abstract: Improving on Restasis?

2012-01-18T22:47:00.000-08:00

Very interesting - investigating a Cyclosporine A prodrug for dry eye. Sure sounds favorable so far.

In vivo characterisation of a novel water-soluble Cyclosporine A prodrug for the treatment of dry eye disease.

Cyclosporine A (CsA) has been demonstrated to be effective for the treatment of a variety of ophthalmological conditions, including ocular surface disorders such as the dry eye disease (DED). Since CsA is characterised by its low water solubility, the development of a topical ophthalmic formulation represents an interesting pharmaceutical question. In the present study, two different strategies to address this challenge were studied and compared: (i) a water-soluble CsA prodrug formulated within an aqueous solution and (ii) a CsA oil-in-water emulsion (Restasis®, Allergan Inc., Irvine, CA). First, the prodrug formulation was shown to have an excellent ocular tolerance as well as no influence on the basal tear production; maintaining the ocular surface properties remained unchanged. Then, in order to allow in vivo investigations, a specific analytical method based on ultra high pressure liquid chromatography coupled with triple quadrupole mass spectrometer (UHPLC-MS/MS) was developed and optimised to quantify CsA in ocular tissues and fluids. The CsA ocular kinetics in lachrymal fluid for both formulations were found to be similar between 15min and 48h. The CsA ocular distribution study evidenced the ability of the prodrug formulation to penetrate into the eye, achieving therapeutically active CsA levels in tissues of both the anterior and posterior segments. In addition, the detailed analysis of the in vivo data using a bicompartmental model pointed out a higher bioavailability and lower elimination rate for CsA when it is generated from the prodrug than after direct application as an emulsion. The interesting in vivo properties displayed by the prodrug solution make it a safe and suitable option for the treatment of DED.

Eur J Pharm Biopharm. 2011 Dec 3. [Epub ahead of print]
Rodriguez-Aller M, Kaufmann B, Guillarme D, Stella C, Furrer P, Rudaz S, El Zaoui I, Valamanesh F, Di Tommaso C, Behar-Cohen F, Veuthey JL, Gurny R.
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Switzerland.

Abstract: Azasite for contact lens dry eye

2012-01-18T22:42:00.000-08:00

OK... so they had one group use Azasite and another group use rewetting drops on their contacts, and the Azasite group was happier. But WHY? Seems crazy to have an endpoint just saying this may make contact lens wearers able to wear their lenses more. Do they have bleph/MGD? What is going on that Azasite improves (and does anything else improve it)?

Safety and Efficacy of Topical Azithromycin Ophthalmic Solution 1.0% in the Treatment of Contact Lens-Related Dry Eye.

Abstract

PURPOSE:
The purpose of this pilot study was to evaluate the safety and efficacy of azithromycin ophthalmic solution 1% in patients with contact lens-related dry eye (CLDE).

METHODS:
This was a 4-week, single-center, open-label clinical trial in patients diagnosed with CLDE using the Contact Lens Dry Eye Questionnaire (CLDEQ). Fifty patients were enrolled in this study. The patients were randomized to 1 of 2 treatment groups: azithromycin ophthalmic solution administered bid on days 1 and 2 and on days 3 to 29±1 or Visine for Contacts rewetting drops administered qid on days 1 to 29±1. The patient diaries were used daily to collect data on comfortable and total contact lens wear time and ocular dryness throughout the treatment period. Tear osmolarity, fluorescein corneal staining, and visual acuity were also assessed during clinic visits.

RESULTS:
Fifty patients were enrolled, and 44 completed the study. One patient discontinued in the azithromycin group, and five patients discontinued in the rewetting drops group because of adverse events. A statistically significant increase in mean comfortable contact lens wear time from baseline was observed for the subjects treated with azithromycin ophthalmic solution as compared with the subjects treated with rewetting drops at week 4 (P=0.004; primary endpoint), in addition to weeks 2 and 3. The improvement in the mean comfortable wear time for the patients in the azithromycin treatment group exceeded 2 hrs throughout the treatment period (weeks 1-4). No significant differences were observed between the groups for total wear time, low contrast visual acuity, or tear osmolarity. Subject-rated ocular dryness (PM time assessments) was significantly improved from baseline in the subjects treated with azithromycin ophthalmic solution as compared with those treated with rewetting drops at weeks 2 and 3 endpoints (P=0.015 for each week). Additionally, a statistical difference was observed in favor of the azithromycin treatment group at week 2 for the subjects reclassifying as nondry eye as determined by the CLDEQ (P=0.05).

CONCLUSIONS:
Treatment with topical azithromycin ophthalmic solution was well tolerated and resulted in a significant improvement in comfortable contact lens wear time in the patients with CLDE.

Eye Contact Lens. 2011 Dec 6. [Epub ahead of print]
Nichols JJ, Bickle KM, Zink RC, Schiewe MD, Haque RM, Nichols KK.
From the College of Optometry (J.J.N., K.K.N.), University of Houston, Houston, TX; Ohio State University College of Optometry (K.M.B.), Columbus, OH; and Inspire Pharmaceuticals (R.C.Z., M.D.S., R.M.H.) Raleigh, NC.

Abstract: Epidermal growth factor

2012-01-18T22:37:00.000-08:00

...in treating BAC-induced dry eye in mice.

Therapeutic Effects of Epidermal Growth Factor on Benzalkonium Chloride-Induced Dry Eye in a Mouse Model.

Purpose
To investigate the therapeutic effects and possible mechanisms of epidermal growth factor (EGF) on the mouse dry eye model induced by Benzalkonium chloride (BAC).

Methods
The eye drop containing EGF was topically administered (3ng/day) on BAC-induced dry eye model. The following clinical indications of dry eye were evaluated on D2, 4 and 6: tear break-up time (BUT), corneal fluorescein staining, inflammatory index and tear volume. Global specimens were collected on D6 and then the following examinations were performed: histological investigation, TUNEL assay to measure the dead cells, periodic acid-schiff (PAS) assay to detect goblet cells, and immunostaining of antibodies of Ki-67, EGF receptor (EGFR) and MUC1 in the corneas. The levels of EGFR and p-ERK of the corneas were also measured by Western blot.

Results
EGF resulted in longer BUTs on D2 and D6, lower fluorescein staining scores on D4 and D6 while no significant changes in inflammatory index or tear volume. EGF induced higher EGFR expression in corneal tissues by immunofluorescent staining and Western blot. EGF also up-regulated p-ERK, increased Ki-67 positive cells and decreased TUNEL positive cells. In addition, EGF significantly increased the goblet cells number and MUC1 expression in the epithelium.

Conclusions
Topical application of EGF presented clinical improvements on dry eye by stabilizing the tear film and maintaining the integrity of epithelium. Our results indicated that EGF had the potential in the clinical treatment of dry eye.

Invest Ophthalmol Vis Sci. 2011 Dec 8. [Epub ahead of print]
Xiao X, He H, Lin Z, Luo P, He H, Zhou T, Zhou Y, Liu Z.
. Eye Institute of Xiamen University, Xiamen, P.R.China.

TearLab FDA status revision

2012-01-18T22:12:00.000-08:00

Good news for TearLab - it's been reclassified such that it will be easier for drs. to adopt. Bet that will help with their marketing machine.

TearLab Gets FDA Approval for Wider Use of Eye Test

The FDA granted a Clinical Laboratory Improvement Amendments to TearLab to widen the use of its Osmolarity System, a test for dry eye, according to a Reuter's report.

The change came after the device was reclassified to "simple" instead of "moderately complex". Previously, an eye practice had to obtain CLIA certification through paperwork and a 20-hour CME course to use the device. Company shares were trading up at much as 80 percent after the announcement.

Abstract: Eyelash extensions - side effects

2012-01-18T22:05:00.000-08:00

According to this study, you can get dry eye or allergic blepharitis from eyelash extensions. A key culprit is formaldehyde in the glues. - There is just no free lunch with eyelash enhancements, is there? Even Latisse has dry eye (among other things) as a side effect.

Ocular disorders due to eyelash extensions.

PURPOSE:
: Eyelash extensions are a beauty treatment in which individual synthetic extensions are applied, lash by lash, to natural eyelashes. The procedure is becoming popular worldwide because they seem more natural and last longer than other types of false eyelashes. However, partly because a bonding agent (glue) containing organic substances is applied near the eyes, consultations with ophthalmologic clinics and the National Consumer Affairs Center of Japan have increased annually. In the present study, we investigated eye disorders due to eyelash extensions.

METHODS:
: Ocular disorders were retrospectively investigated in 107 women (age 21-52 years) who visited ophthalmologic clinics in Japan with complaints of eye symptoms resulting from eyelash extensions between March 2007 and March 2010. The patients had no history of eye diseases. Of the patients 42 were 21 to 29 years of age, 44 were 30 to 39 years, 19 were 40 to 49 years, and 2 were 50 to 60 years. Three glues, the ingredients of which are not disclosed, were chemically analyzed for detection of more than 70 substances suspected to be ingredients.

RESULTS:
: The ocular disorders due to eyelash extensions included keratoconjunctivitis due to invasion of glue or removing agents in 64 patients, allergic blepharitis due to glues in 42 patients (4 of these patients developed both keratoconjunctivitis and allergic blepharitis), conjunctival erosion due to eyelid-fixing tapes in 3 patients, allergic blepharitis due to eyelid-fixing tapes in 1 patient, and subconjunctival hemorrhage due to compression during removal of extensions in 1 patient. In all 107 patients, the symptoms were resolved by adequate treatments with eye drops and/or ointments. Ingredient analysis detected formaldehyde in concentrations above the standard threshold level in all 3 glues. In addition, lead and benzoic acid were also detected; however, concentrations of these particular compounds were low and therefore unlikely to cause disorders in humans.

CONCLUSIONS:
: Eyelash extension procedures may cause ocular disorders, such as keratoconjunctivitis and allergic blepharitis; indeed, all glues for eyelash extensions analyzed in the present study contained formaldehyde, which can cause keratoconjunctivitis. From the viewpoint of hygienics, it is necessary to disinfect devices, provide handling instructions for organic solvents, improve glue ingredients, and improve the ophthalmologic knowledge of the practitioners.

Cornea. 2012 Feb;31(2):121-5.
Amano Y, Sugimoto Y, Sugita M.
From the *Department of Ophthalmology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan; †Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan; and ‡Eikokai Medical Foundation, Nakameguro Eye Hospital, Tokyo, Japan.

Blurb: Eye drops making eyes worse

2012-01-18T21:57:00.000-08:00

I ran across this article by Dr. Mark Sherman in MDNews.com and really appreciated it. The idea that a prescription drop could make you worse, not better, is far too often overlooked altogether by doctor and patient. We really need to observe carefully the effects of anything we're taking.

When Eye Drops Make the Red Eye Worse
by Mark Sherman MD

It happens at least once a week. A patient is referred to an ophthalmologist for management of an eye infection, which appeared to be improving with use of topical antibiotic eye drops only to reverse its course and become progressively worse.

What does the ophthalmologist recommend? Stop everything? At least for a few days, consider stopping all eye drops and, under close observation, determine whether it is, in fact, recurrence of the infection or, perhaps, secondary irritation caused by toxicity of the initial eye drops.

Eye drops are the foundation of treatment for the most common ocular disorders, including allergy, infection, dry eye, glaucoma and uveitis. Patients who undergo routine cataract surgery are prescribed eye drops for the pre-, intra- and postoperative periods. What makes it possible to use these eye drops through an entire course of treatment is the preservative contained in the bottle, in addition to the therapeutic agent and vehicle. The preservatives used in most multiuse topical ophthalmic products have been used for decades. Preservatives are essential for the safe and efficient treatment of most ocular disorders. However, an eye problem that initially improves and then worsens may be a red flag pointing to the potential for ocular toxicity caused by some preservatives.

Toxicity of a preservative refers to the chemical action of the preservative that leads to damage to or disturbance of function of any of the ocular surface structures. Virtually all premixed, multidose eye drops contain a preservative or preservative system to prevent microbial overgrowth....

Abstract: Restasis in Korea

2012-01-18T21:54:00.000-08:00

(stifling a yawn)

Cyclosporine 0.05% ophthalmic emulsion for dry eye in Korea: a prospective, multicenter, open-label, surveillance study.

PURPOSE:
To assess the effectiveness and tolerability of cyclosporine ophthalmic emulsion (CsA) 0.05% in patients with moderate to severe dry eye disease in Korea.

METHODS:
This was a prospective, multicenter, open-label, surveillance study of 392 Korean patients with moderate to severe dry eye disease who were treated with CsA 0.05% for three months. An assessment of effectiveness was performed at baseline, and after 1, 2, and 3 months. The primary effectiveness outcomes were changes in ocular symptoms and Schirmer score. The secondary effectiveness outcomes were a change in conjunctival staining, use of artificial tears, global evaluation of treatment, and patient satisfaction. The primary safety outcome was the incidence and nature of adverse events.

RESULTS:
A total of 362 patients completed the study. After three months, all ocular symptom scores were significantly reduced compared to the baseline values, while the Schirmer scores were significantly increased relative to baseline (p < 0.0001). After three months, there were significant reductions from baseline in conjunctival staining (p < 0.01) and use of artificial tears (p < 0.0001). According to clinicians' global evaluations, most patients (>50%) experienced at least a 25% to 50% improvement in symptoms from baseline at each follow-up visit. The majority of patients (72.0%) were satisfied with the treatment results, and 57.2% reported having no or mild symptoms after treatment. The most common adverse events were ocular pain (11.0%).

CONCLUSIONS:
Our findings indicate that CsA 0.05% is an effective and tolerable treatment for dry eye disease in Korean clinical practice.

Korean J Ophthalmol. 2011 Dec;25(6):369-74. Epub 2011 Nov 22.
Byun YS, Rho CR, Cho K, Choi JA, Na KS, Joo CK.
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Abstract: Pregnancy & dry eye

2012-01-18T21:49:00.000-08:00

My dry eyes got a lot worse during pregnancy. There's a ton of literature about the hormonal causes of dry eye but not a lot on pregnancy. Even though this study's just about bunnies, it's nice to have something this firm.

Changes of the ocular surface and aquaporins in the lacrimal glands of rabbits during pregnancy.

PURPOSE:
To test the hypotheses that pregnancy represents a physiologic condition that is associated with dry eye symptoms, and the expression of aquaporin 4 (AQP4) and AQP5 are altered in the lacrimal gland (LG) from term pregnant rabbits.

METHODS:
Schirmer's test, tear break-up time (BUT), and Rose Bengal staining were used to evaluate ocular surface health. LG were obtained from term pregnant rabbits and age-matched female control rabbits and then processed for laser capture microdissection (LCM), real time RT-PCR, western blot, and immunofluorescence for the detection and quantification of mRNA and proteins of AQP4 and AQP5.

RESULTS:
Pregnant rabbits demonstrated typical clinical symptoms of dry eye, including decreased Schirmer score and BUT as well as increased Rose Bengal staining of cornea. In term pregnant rabbits, mRNA for AQP5 from whole LG was significantly lower than that of control rabbits, while mRNA for AQP4 was not. Levels of mRNA for AQP4 and AQP5 underwent significant changes in acini and epithelial cells from specific duct segments during pregnancy. Western blot from whole LG lysates demonstrated that expression of AQP4 was 24% more abundant in term pregnant rabbits while AQP5 was 22% less when compared to control rabbits respectively. At term pregnancy, AQP4 immunoreactivity (AQP4-IR) was increased in acini while its intensity remained the same in ducts. AQP5-IR was present in both apical and basolateral membranes of acinar cells in normal control and pregnant rabbits, while ductal cells in pregnant rabbits also showed significant amount of AQP5-IR.

CONCLUSIONS:
The data presented here demonstrated significant dry eye symptoms in pregnant rabbits. Our data also showed altered expressions of AQP4 and AQP5 during pregnancy and suggested that these changes may contribute to the altered LG secretion and dry eye symptoms during pregnancy.

Mol Vis. 2011;17:2847-55. Epub 2011 Nov 9.
Ding C, Lu M, Huang J.
Department of Cell and Neurobiology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089-9112, USA. cding@usc.edu

Abstract: Challenges in the clinical measurement of OSD in glaucoma patients.

2012-01-18T21:44:00.000-08:00

It's nice to see a couple of the best known names in dry eye worldwide directing attention to dry eye in glaucoma patients. I'm not sure why clinically measuring OSD in glaucoma patients could be any different than in any other patient, but its always good to see some attention focused on the importance of diagnosing it.

Challenges in the clinical measurement of ocular surface disease in glaucoma patients.

Ocular surface disease (OSD) is common among glaucoma patients. Clinical assessment of OSD can be challenging. This review focuses on some of the limitations relating to both subjective and objective measures of OSD, including dry eye. A survey of the literature was conducted to identify the caveats associated with different methods of assessing OSD. The effect of preservatives on the ocular surface, with respect to glaucoma patients in particular, was also reviewed. Objective methods for assessing ocular surface health and disease include the Schirmer test, tear break-up time, fluorescein turnover, corneal and conjunctival staining, tear osmolarity, and vital dyes. These measures all have limitations in terms of their ability to grade the severity of OSD. Previous studies using the OSD Index showed a mild-to-moderate correlation to dry eye disease severity. Other scoring systems for dry eye have shown a relationship to patient symptom scores or quality of life. Due to the challenges clinicians face concerning both subjective and objective ocular surface health assessments, discerning clinical improvement in ocular surface disease can be a challenge. Further research is needed in order to optimize existing clinical methods and/or identify alternative techniques for assessing OSD in the glaucoma population.

Clin Ophthalmol. 2011;5:1575-83. Epub 2011 Nov 1.
Pflugfelder SC, Baudouin C.
Ophthalmology-Ocular Surface Center, Baylor College of Medicine, Houston, TX, USA.

Abstract: Demodex and blepharitis

2012-01-18T21:33:00.000-08:00

Bacillus oleronius and Demodex mite infestation in patients with chronic blepharitis.

To better recognize the pathogenicity of ocular Demodex mites, we analysed Bacillus oleronius infection in patients with Demodex-related chronic blepharitis. The studies were conducted on 68 adult patients, in whom ophthalmological and parasitological tests permitted the distinction of a group of 38 patients with a diagnosis of Demodex-related chronic blepharitis (group 1, including a subgroup 1a with moderate blepharitis and a subgroup 1b with severe blepharitis) and a group of 30 healthy individuals (group 2). In every person studied six eyelashes were epilated from each eye and the number of Demodex per eyelash was scored. In parallel, bacterial culture and isolation allowed their phenotypic and molecular identification. The drug sensitivity of the isolates was tested using E-tests. Intensity of Demodex infestation showed no significant differences between subgroups 1a and 1b. From the epilated eyelashes 23 bacterial isolates were obtained, identified as being B. oleronius. All the studied strains were sensitive to ciprofloxacin, doxycycline and gentamicin. The Demodex mite represents an independent aetiopathogenetic factor in blepharitis. In parallel, the parasite may act as a carrier of B. oleronius bacteria, which most probably function as a co-pathogen in the development of severe forms of blepharitis.

Clin Microbiol Infect. 2011 Oct 21. doi: 10.1111/j.1469-0691.2011.03704.x. [Epub ahead of print]
Szkaradkiewicz A, Chudzicka-Strugała I, Karpiński TM, Goślińska-Pawłowska O, Tułecka T, Chudzicki W, Szkaradkiewicz AK, Zaba R.
Department of Medical Microbiology, University of Medical Sciences Department of Ophthalmology, 111 Military Hospital Department of Conservative Dentistry and Periodontology, University of Medical Sciences Clinic of Dermatology, University of Medical Sciences, Poznan, Poland.

Abstract: Corneal fluorescein staining correlates with visual function in dry eye patients.

2012-01-18T21:30:00.000-08:00

Corneal fluorescein staining correlates with visual function in dry eye patients.

Purpose.
To investigate the changes in functional visual acuity (VA) and higher order aberrations in dry eye patients.

Methods.
In this prospective comparative case series, 22 right eyes were classified into those with or without superficial punctate keratopathy (SPK) in the central cornea of 22 patients with Sjögren syndrome; 10 right eyes of 10 normal subjects served as the control. Serial measurements of VAs using a functional VA measurement system and higher order aberrations using a wavefront sensor were performed under blink-free conditions without topical anesthesia over a 10-second period. The parameters for each measurement were compared among the SPK-positive and -negative and normal groups. The correlation between those parameters was also analyzed.

Results.
Dry eye with SPK showed significant deterioration of visual function and optical quality compared with dry eye without SPK and in normal eyes, as detected by both the visual maintenance ratio (VMR; P < 0.05) and the variation of VA (P < 0.05) and by comalike and total higher order aberrations (P < 0.05). Moreover, the severity of epithelial damage at the central cornea correlated significantly with VMR (P < 0.01) and variation of VA (P < 0.01) as well as comalike (P < 0.05) and total higher order aberrations (P < 0.05). The dry eye group without SPK showed minor visual deterioration compared with normal eyes, as detected only by VMR (P < 0.05).

Conclusions.
Optical disturbances at the central optical zone of the cornea in dry eye disease may affect visual performance. Functional VA measurement may be an applicable method of evaluating visual performance in dry eyes that is as efficient as wavefront aberration measurements.

Invest Ophthalmol Vis Sci. 2011 Dec 16;52(13):9516-22. Print 2011.
Kaido M, Matsumoto Y, Shigeno Y, Ishida R, Dogru M, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Abstract: Long term effect of si-hy contacts

2012-01-18T21:24:00.000-08:00

Purpose.
To evaluate ocular surface changes in long-term silicone hydrogel contact lens wearers.

Methods.
Thirty patients were included in this study. Twenty patients (40 eyes) using contact lenses constituted group 1 and 10 (20 eyes) volunteers constituted group 2. The duration of average contact lens usage was 7.74±3.3 years. Ocular surface was evaluated by surface staining, tear film break-up time (TBUT), Schirmer I test, and conjunctival impression cytology with color-coded mapping technique and by the Ocular Surface Disease Index (OSDI).

Results.
The mean break-up time was lower and staining scores were higher in group 1 (p<0.001) but Schirmer values were not significantly different from group 2 (p>0.05). The mean OSDI score was 34.59±11.93 to 19.28±6.7 in group 1 and 2. Increased metaplastic predominant changes of grade II and III were observed in the interpalpebral and perilimbal areas in group 1. Significant correlations were observed in TBUT, cornea staining, and grade II to grade III metaplasia ratios between duration of the lens usage and contact lens wear time in a day.

Conclusions.
Silicone hydrogel lenses produce significant changes on tear film and impression cytology of the ocular surface in long-term use.

Eur J Ophthalmol. 2011 Nov 11:0. doi: 10.5301/ejo.5000079. [Epub ahead of print]
Sengor T, Aydin Kurna S, Ozbay N, Ertek S, Aki S, Altun A.
Ophthalmology Clinic, Fatih Sultan Mehmet Education and Training Hospital, Istanbul - Turkey.

Drug news: CF101 starts enrolling for Phase III trial

2012-01-18T21:08:00.000-08:00

Finally, some news on CF101. Purchased in November by Denali Concrete Management, and as of December started enrolling for the Phase III trial. Ambitious endpoint.

Denali Concrete Management Inc. Announces the Commencement of Patient Enrollment for the Phase 3 Dry Eye Syndrome Study

Denali Concrete Management Inc. DCMG announced today that it has commenced patient enrollment for a phase 3 clinical study of the safety and efficacy of CF101, daily administered orally, in patients with moderate-to-severe Dry Eye Syndrome. This multi-center clinical trial is conducted in the United States, Europe and Israel. The randomized, double-masked clinical trial will include 231 patients who will be randomized to receive 2 doses of CF101 and Placebo, for a period of 24 weeks. The primary efficacy endpoint will be complete clearing of corneal staining....

Abstract: Mucin, protein levels elevated in postmenopausal women with dry eye

2012-01-18T21:05:00.000-08:00

Comparison of mucin levels at the ocular surface of postmenopausal women with and without a history of dry eye.

PURPOSE:
To determine if levels of the glycocalyx membrane mucins, MUC1 and MUC16, and the secreted goblet cell mucin MUC5AC are altered in conjunctival cells and tears of postmenopausal women presenting with a history of non-Sjögren dry eye and if mucin levels correlate with dry eye clinical diagnostic data.

METHODS:
Eighty-four postmenopausal women with a history of non-Sjögren dry eye and 30 normal subjects were recruited for this study. Impression cytology samples were collected for mucin messenger RNA (mRNA) and protein analysis. Tears were collected for mucin protein assay. Quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were used to quantitate MUC1, MUC16, and MUC5AC levels.

RESULTS:
Postmenopausal women with a history of dry eye displayed significantly increased MUC1 mRNA expression and cellular protein compared with normal subjects (P < 0.001 and P < 0.01, respectively). Similarly, cellular MUC16 protein levels were significantly higher (P < 0.001). Mucin levels were found to be correlated with the clinical characterization of the subjects, including staining and symptoms. Although cellular MUC5AC protein levels were increased in symptomatic subjects, the increase did not reach statistical significance.

CONCLUSIONS:
Elevation in MUC1 and MUC16 mRNA and/or protein levels in postmenopausal women with non-Sjögren dry eye with a history of dry eye may be a compensatory response to irritation and inflammation associated with the disease. Understanding the pattern of mucin expression associated with the dry eye pathology may clarify factors involved in the progression of the disease and enhance the development of targeted therapies.

Cornea. 2011 Dec;30(12):1346-52.
Gipson IK, Spurr-Michaud SJ, Senchyna M, Ritter R 3rd, Schaumberg D.
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. Ilene.gipson@schepens.harvard.edu

Drug news: R-Tech Ueno to use Albucult (albumin) as dry eye drug

2012-01-18T20:23:00.000-08:00

Novozymes Biopharma announced R-Tech Ueno (Japanese company) will be using Albucult in a dry eye drug.

Albucult is albumin, a component of serum (aka autologous serum eyedrops). I've posted about it once or twice in the past. It's also been listed on R-Tech Ueno's site for a long time so I'm not sure why it's news but hopefully it means it's going to get studied, which would be GREAT.

Novozymes Biopharma supplies R-Tech Ueno with Albucult® for use in unique dry eye therapy

November 15, 2011 – Novozymes Biopharma, part of Novozymes A/S world leader in bioinnovation, has announced that its recombinant human albumin, Albucult®, has been selected by R-Tech Ueno for use in a unique treatment for dry eye syndrome....

Abstract: Canine neurogenic KCS

2012-01-18T20:09:00.000-08:00

Most of us aren't here to talk about canine dry eye but every now and then something comes up in the veterinary literature that looks interesting in some way. I was just intrigued to see this "neurogenic KCS" diagnosis, which is not something I come across in hearing of humand dry eye diagnosis. In fact other than extremes (like a cornea with severely reduced sensitivity) and Perry Rosenthal's work I don't hear much about the nervous system and dry eye. Nor was this abstract particularly enlightening but I thought I'd post it. Googling on the topic brought up a rather good overview by a veterinarian.

Canine neurogenic Keratoconjunctivitis sicca: 11 cases (2006-2010).

Objective
To describe the clinical data of dogs with neurogenic Keratoconjunctivitis sicca (KCS) and an ipsilateral dry nose without other neurologic deficits.

Procedure
The retrospective case study included 11 dogs diagnosed with neurogenic KCS and an ipsilateral dry nose between 2006 and 2010. Medical records were reviewed for breed, age, sex, history, suspected cause of neurogenic KCS, clinical signs, and treatment modalities. Follow-up information was obtained by re-examination of patients or completion of a telephone survey with the referring veterinarian or the owners.

Results
Mean age of the dogs was 6.6 ± 4.5 years. Neurogenic KCS was diagnosed in three females, five spayed females, one male, and two castrated males representing 10 different breeds. Ophthalmic signs of KCS (mean Schirmer tear test [STT] value of 1.9 ± 2.9 mm/min) combined with an ipsilateral dry nose were diagnosed in seven left and four right eyes. The suspected cause of neurogenic KCS was idiopathic in nine and trauma in two cases. Systemic therapy consisted of oral pilocarpine 1-2% eye drops combined with case-specific topical treatment with cyclosporine 0.2% and tear substitutes. Duration of systemic treatment with pilocarpine until healing was 125 days (range 84-204, median 98 days) for five dogs. One dog was lost to follow-up, and the remaining five dogs are still under systemic treatment with pilocarpine.

Conclusions
Neurogenic KCS with an ipsilateral dry nose seems to be a predominantly idiopathic disease of middle-aged female dogs without breed predisposition, which may be self-limiting in some cases.

Vet Ophthalmol. 2011 Oct 31. doi: 10.1111/j.1463-5224.2011.00968.x. [Epub ahead of print]
Matheis FL, Walser-Reinhardt L, Spiess BM.
Equine Department, Section of Ophthalmology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.

Abstract: Salivary gland transplant for dry eye

2012-01-18T19:55:00.000-08:00

Another variation on salivary gland transplant (reduced submandibular gland transplant).

An experimental study of the management of severe keratoconjunctivitis sicca with autologous reduced-sized submandibular gland transplantation.

We have evaluated transplantation of reduced submandibular glands for the treatment of severe keratoconjunctivitis sicca. Thirty-four rabbits were allocated into three groups: dry eye (controls, n=10), transplantation of whole submandibular glands (n=12), and transplantation of reduced submandibular glands (n=12). Outcome measures included the results of Schirmer's test and the Rose Bengal test, and histological examination of the cornea and the transplanted gland. Volume of tears significantly increased after transplantation of the whole gland, but did not change after transplantation of the reduced gland compared with dry eyes induced preoperatively. Neither transplantion group had keratoconjunctivitis sicca postoperatively. There were no histological abnormalities in the transplanted tissues. The results that the surgical technique of using reduced submandibular glands for transplantation was feasible, and that the secretion from the reduced gland was similar to that from a normal lacrimal gland. In conclusion, transplantation of a reduced submandibular glands is feasible in the treatment of keratoconjunctivitis sicca.

Br J Oral Maxillofac Surg. 2011 Nov 1. [Epub ahead of print]
Ge XY, Yu GY, Fu J, Wu DC, Zhang XX, Wang YX, Li SL.
Department of Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun Nandajie, Haidian District, Beijing, China.

Abstract: Severity of dry eye dependent on source of stem cells in transplantation

2012-01-18T19:37:00.000-08:00

In this study, patients with various types of stem cell transplants had dry eye outcomes that correlated to some degree with the type of transplantation they had. Dry eye tended to show up quite late in the peripheral blood stem cell transplantation patients.

Comparison of stem cell sources in the severity of dry eye after allogeneic haematopoietic stem cell transplantation.

AIMS:
To compare the incidence and severity of dry eye (DE) after allogeneic haematopoietic stem cell transplantation (HSCT) according to the stem cell source. The authors specifically focused on patients who received bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT) and cord blood transplantation (CBT).

METHODS:
Ninety-nine HSCT recipients who were prospectively followed-up for at least 100 days at Keio University Hospital were recruited. Ophthalmological examinations included evaluation of ocular surface findings and tear dynamics. The data on systemic graft-versus-host disease were collected by chart review.

RESULTS:
Of the 99 patients (BMT, 67; PBSCT, 18; CBT, 14), 42 developed DE or showed worsened pre-existing DE after HSCT; 31 (46.3%) BMT group; 8 (44.0%) PBSCT group; and 3 (21.4%) CBT group (p=0.78). The median onset time of DE tended to be later in the PBSCT group (474 days, range 95-1559) than in the BMT (287 days, range 67-1216) or CBT (168 days, range 33-481) group, but the difference was not significant (p=0.23). However, the proportion of patients with severe DE was significantly higher in the PBSCT group (N=7, 87.5%) than in the BMT (N=12, 38.7%) or CBT (N=1, 33.3%) group (p=0.04) and CBT showed the lowest among all three stem cell sources.

CONCLUSION:
The data in this study suggested that the severity and onset time of DE were affected by the stem cell source. Close attention must be paid to the development of late-onset severe DE in PBSCT recipients.

Br J Ophthalmol. 2012 Jan;96(1):34-7. Epub 2011 Nov 3.
Uchino M, Ogawa Y, Uchino Y, Mori T, Okamoto S, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo, Japan.

Drug news: Mixed results from RegeneRx clinical trials

2012-01-18T19:10:00.000-08:00

On Nov. 4th, RegeneRx Biopharma announced results of their 30-day clinical trial. The drug failed to meet either of the two primary outcome measures they were targeting; however, they did identify some sign & symptom improvements. A follow-up press report clarified their position on this and a report put out on Jan 5th indicates they will be shifting the focus of further research on the drug.

While the study did not meet the two primary outcome measures selected prior to the beginning of the trial, statistically significant sign and symptom improvements attributable to RGN-259 were identified. We believe these sign and symptom improvements are clinically relevant endpoints that would be acceptable outcome measures for future pivotal trials, which we intend to confirm with FDA at a post-Phase 2 meeting.

I'm back!

2012-01-18T18:49:00.000-08:00

Sorry to have dropped out of sight for so long... just one of those times when life intervenes for awhile. Moving house, farm, & business kept us busy for awhile, among other things. We are mostly all settled now (family, business, sheep, chickens, dog, cats, did I miss anything?) and getting back to business. I have about 2.5 months of news to catch up on and I plan to cover that over the next couple of days, so stay tuned.

Rebecca

Abstract: Meibum lipid composition in asians with DED

2011-11-02T09:38:00.000-07:00

Meibum lipid composition in asians with dry eye disease.

BACKGROUND:
Previous lipidomic analyses of the human meibum had largely focused on individuals from non-Asian populations, despite the higher prevalence of dysfunctional tear syndrome (DTS) observed across Asia. Information pertaining to the alterations in lipid profiles in relation to DTS onset and progression is also lacking and warrants comprehensive experimental analysis. METHODOLOGIES/

PRINCIPAL FINDINGS:
We examined the meibum lipidome of 27 DTS patients and 10 control subjects for a total of 256 lipid species from 12 major lipid classes, including cholesteryl ester (CE), wax ester (WE), triacylglyceride (TAG), (O-acyl)-ω-hydroxy fatty acid (OAHFA), glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG) and sphingolipids (sphingomyelin, SM; ceramide, Cer; glucosylceramide, GluCer; dihexosylceramide, DihexCer). Neutral lipids were analysed using high-performance liquid-chromatography coupled with mass spectrometry (HPLC/MS) and tandem mass spectrometry (MS/MS) was used for the qualitative and quantitative analysis of polar lipid species. DTS patients were classified into three severity groups (i.e. mild, moderate and severe) based on the ocular surface disease index (OSDI). A significantly lower level of TAG (p<0.05) was observed in patients under the moderate category compared to the mild category. Notably, a number of OAHFA species displayed consistently decreasing levels that correlate with increasing disease severity. An attempt was also made to investigate the changes in meibum lipid profiles of DTS patients compared to normal individuals classified based on OSDI score. Several unsaturated TAG and PC species were found at significantly higher levels (p<0.05) in patients than controls.

CONCLUSION:
The current study presents, for the first time, a comprehensive lipidome of meibum from individuals of an Asian ethnicity, which can potentially offer new insights into the higher prevalence of DTS observed amongst Asian populations. This study also represents an attempt towards identification of lipid species in meibum which could serve as marker for DTS.

PLoS One. 2011;6(10):e24339. Epub 2011 Oct 17.
Lam SM, Tong L, Yong SS, Li B, Chaurasia SS, Shui G, Wenk MR.
Source
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

Abstract: Once again, dry eye gets short shrift in LASIK studies

2011-10-31T09:12:00.001-07:00

I guess I'm on the warpath this morning.

Refractive surgery research at its best.

This abstract...

1) Purports to assess dry eye amongst its outcome measures (after all, it's the #1 complication so they'd better pay it lip service)
2) Then it uses the most unreliable not to mention barbaric method to evaluate dry eye (Schirmer)
3) Then it doesn't tell us what the dry eye results were, because naturally, only vision matters.

Come on guys, surely you can do better than this.

A prospective, randomized, fellow eye comparison of WaveLight Allegretto Wave Eye-Q versus VISX CustomVue™ STAR S4 IR™ in laser in situ keratomileusis (LASIK): analysis of visual outcomes and higher order aberrations.

PURPOSE:
To compare outcomes in visual acuity, refractive error, higher-order aberrations (HOAs), contrast sensitivity, and dry eye in patients undergoing laser in situ keratomileusis (LASIK) using wavefront (WF) guided VISX CustomVue and WF optimized WaveLight Allegretto platforms.

METHODS:
In this randomized, prospective, single-masked, fellow eye study, LASIK was performed on 44 eyes (22 patients), with one eye randomized to WaveLight Allegretto, and the fellow eye receiving VISX CustomVue. Postoperative outcome measures at 3 months included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive error, root-mean-square (RMS) value of total and grouped HOAs, contrast sensitivity, and Schirmers testing.

RESULTS:
Mean values for UDVA (logMAR) were -0.067 ± 0.087 and -0.073 ± 0.092 in the WF optimized and WF guided groups, respectively (P = 0.909). UDVA of 20/20 or better was achieved in 91% of eyes undergoing LASIK with both lasers while UDVA of 20/15 or better was achieved in 64% of eyes using the Allegretto platform, and 59% of eyes using VISX CustomVue (P = 1.000). In the WF optimized group, total HOA increased 4% (P = 0.012), coma increased 11% (P = 0.065), and spherical aberration increased 19% (P = 0.214), while trefoil decreased 5% (P = 0.490). In the WF guided group, total HOA RMS decreased 9% (P = 0.126), coma decreased 18% (P = 0.144), spherical aberration decreased 27% (P = 0.713) and trefoil decreased 19% (P = 0.660). One patient lost one line of CDVA secondary to residual irregular astigmatism.

CONCLUSION:
Both the WaveLight Allegretto and the VISX CustomVue platforms had equal visual and safety outcomes. Most wavefront optimized HOA values trended upward, with a statistically significant increase in total HOA RMS. Eyes treated with the WF guided platform showed a decreasing trend in HOA values.

Clin Ophthalmol. 2011;5:1339-47. Epub 2011 Sep 20.
Moshirfar M, Betts BS, Churgin DS, Hsu M, Neuffer M, Sikder S, Church D, Mifflin MD.
Source
John A Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA.

Abstract: Video TFBUT method versus classic method

2011-10-31T09:06:00.000-07:00

This is an interesting discussion of ways to capture TBUT.

Measurement of ocular surface protection under natural blink conditions.

PURPOSE:
To evaluate a new method of measuring ocular exposure in the context of a natural blink pattern through analysis of the variables tear film breakup time (TFBUT), interblink interval (IBI), and tear film breakup area (BUA).

METHODS:
The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured under forced-stare conditions by an examiner using a stopwatch, while IBI is measured as the subject watches television. The new methodology (video capture manual analysis [VCMA]) involves retrospective analysis of video data of fluorescein-stained eyes taken through a slit lamp while the subject watches television, and provides TFBUT and BUA for each IBI during the 1-minute video under natural blink conditions. The FS and VCMA methods were directly compared in the same set of dry-eye subjects. The VCMA method was evaluated for the ability to discriminate between dry-eye subjects and normal subjects. The VCMA method was further evaluated in the dry eye subjects for the ability to detect a treatment effect before, and 10 minutes after, bilateral instillation of an artificial tear solution.

RESULTS:
Ten normal subjects and 17 dry-eye subjects were studied. In the dry-eye subjects, the two methods differed with respect to mean TFBUTs (5.82 seconds, FS; 3.98 seconds, VCMA; P = 0.002). The FS variables alone (TFBUT, IBI) were not able to successfully distinguish between the dry-eye and normal subjects, whereas the additional VCMA variables, both derived and observed (BUA, BUA/IBI, breakup rate), were able to successfully distinguish between the dry-eye and normal subjects in a statistically significant fashion. TFBUT (P = 0.034) and BUA/IBI (P = 0.001) were able to distinguish the treatment effect of artificial tears in dry-eye subjects.

CONCLUSION:
The VCMA methodology provides a clinically relevant analysis of tear film stability measured in the context of a natural blink pattern.

Clin Ophthalmol. 2011;5:1349-57. Epub 2011 Sep 22.
Abelson R, Lane KJ, Angjeli E, Johnston P, Ousler G, Montgomery D.
Source
Arizona State University, Tempe, AZ, USA.

A Monday morning rant on LASIK, ARSC and dry eye

2011-10-31T08:26:00.000-07:00

The American Refractive Surgery Council Discusses How Advances in LASIK Open Door for Those Once Ineligible

DALLAS, TX -- (Marketwire) -- 10/28/11 -- LASIK was once off-limits to people with thin corneas, dry eye and prescriptions in higher ranges. But thanks to advances in technology and technique, many of those once ineligible for LASIK may now benefit from the popular vision correction procedure....

LAsik,LAsik, RAH RAH RAH!

Classic propaganda on a Monday morning, before I've even had my first cup of coffee. Oops (slap) I forgot, back to green tea.

Fifteen plus years into LASIK, when we've had all this time to study what is well known to be its #1 long-term complication (dry eye), who gets it worst and why... you'd think we would acquire this knowledge and use it to narrow the candidate pool so as to exclude those at highest risk.

Nope. Been there, done that - after all, we kinda-sorta agreed years ago not to push symptomatic people with Sjogrens or RA into LASIK, and to offer PRK instead to a few other people that we think might be high risk, right? That oughta shut up the naysayers.

And we know people everywhere with dry eye are pining to get LASIK, and we want to serve the public well, right? So this is no time to be cautious! It's time to EXPAND the candidate pool. Those fancy new dry eye tests can all be used as part of a bold new marketing plan to show how much you care by identifying people with pre-existing dry eye , explaining how great your technology is at not inducing dry eye, and plying them with steroids and Restasis for awhile before surgery.

Viola. Dry eye? No problem. You Too can benefit from the delights of LASIK! After all, my fancy schmancy femtosecond laser is the latest and greatest and Studies Have Shown* that those don't create as much dry eye as microkeratomes.

Come on guys. You are so blooming predictable. LASIK revenues plummet in an economy like this, and everyone gets more aggressive with the marketing - at what cost?

*well okay maybe not this one.

Abstract: Pollution and the tear film

2011-10-28T13:05:00.000-07:00

Can air pollution affect tear film stability? A cross-sectional study in the aftermath of an explosion accident.

BACKGROUND:
After an explosion and fire in two tanks containing contaminated oil and sulphur products in a Norwegian industrial harbour in 2007, the surrounding area was polluted. This caused an intense smell, lasting until the waste was removed two years later. The present study reports examinations of tear film break up time among the population. The examinations were carried out because many of the people in the area complained of sore eyes. The purpose of the study was to assess the relationship between living or working close to the polluted area and tear film stability one and a half years after the explosion.

METHODS:
All persons working or living in an area less than six kilometres from the explosion site were invited to take part in the study together with a similar number of persons matched for age and gender living more than 20 kilometres away. Three groups were established: workers in the explosion area and inhabitants near the explosion area (but not working there) were considered to have been exposed, and inhabitants far away (who did not work in the explosion area) were considered to be unexposed. A total of 734 people were examined, and the response rate was 76 percent. Tear film stability was studied by assessing non-invasive break-up time (NIBUT) using ocular microscopy. In addition Self-reported Break Up Time (SBUT) was assessed by recording the time the subject could keep his or hers eyes open without blinking when watching a fixed point on a wall. Background information was obtained using a questionnaire. Non-parametric Wilcoxon-Mann-Whitney-tests with exact p-values and multiple logistic regression analyses were performed.

RESULTS:
Both NIBUT and SBUT were shorter among the male exposed workers than among the inhabitants both near and far away from the explosion area. This was also found for SBUT among males in a multiple logistic regression analysis, adjusting for age and smoking.

CONCLUSIONS:
Reduced tear film stability was found among workers in an area where an explosion accident had occurred.

BMC Public Health. 2011 Apr 14;11:235.
Moen BE, Norbäck D, Wieslander G, Bakke JV, Magerøy N, Granslo JT, Irgens A, Bråtveit M, Hollund BE, Aasen T.
Source
Occupational and Environmental Medicine, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. bente.moen@isf.uib.no

Abstract: Rheumatoid arthritis and dry eye

2011-10-28T13:03:00.000-07:00

[Ocular involvement and its' manifestations in rheumatoid arthritis patients].
[Article in Hebrew]

PURPOSE:
To study the type, occurrence and nature of ocular involvement amongst patients with rheumatoid arthritis (RA), and to identify demographic, clinical and/or laboratory variables associated with eye involvement in RA. RESEARCH TYPE: Cross sectional research, retrospective

METHODS:
The research was conducted among 61 patients diagnosed with rheumatoid arthritis. The subjects were recruited for the research during their periodic visits to the Soroka Hospital Rheumatology Clinic. Comprehensive rheumatologic tests were administered and general health was examined with a prepared questionnaire. Additionally, the subjects' personal files were examined with data collected from general serum rheumatologic tests and details regarding medications administered. The patients were given a comprehensive eye examination, including a visual acuity examination, test for anterior and posterior fragments, a slit lamp examination after pupil dilation, for epithelial cell filaments, tests for dry eye symptoms, including a Schirmer's test, a tear breakup time test, and a corneal examination for epithelial cells and the existence of superficial punctate keratopathy. The subjects were also questioned regarding their dry eye syndrome and a specular microscopy test was performed. The assembled data was processed and analyzed with the aim of finding correlations between the subjective and objective sensations of dry eye symptoms and the activity of rheumatoid arthritis disease, blood tests, medications taken, and the patient's general state of health.

RESULTS:
The majority of the research subjects (90.2%) were women. Their average age was 51.9 +/- 13.21 years; 31.1% of the subjects complained of eye dryness and, during the eye examination, 85% were found to be suffering from dry eye. The study found a correlation between the objective indicators of keratitis sicca and the following parameters: laboratory values for SGOT (p < 0.03), ESR (p < 0.05), Cr (p < 0.05), TG (p < 0.03), LDL (p < 0.02), Hb (p < 0.01), ALP (p < 0.01), in addition to prednisone medication (p < 0.03, df = 2, x2 = 7.02) and methotrexate (p < 0.03, df = 2, x2 = 8.88). No correlation was found with the following parameters: age, disease duration, smoking, disease severity, other background diseases, and additional laboratory findings including RF and ANA measurements, and consuming other anti-rheumatoid arthritis medications. Similarly, no relation was found with the patients' various subjective syndromes. The average results of the specular microscopy test were 2116.15 +/- 416.59 for the right eye and 2125.67 +/- 446.14 for the left eye.

CONCLUSIONS:
The significance of the specular microscopy test results is that corneal damage found in rheumatoid arthritis patients occurs only to the external layer and does not affect the endothelial layer. The study indicates that keratitis sicca is prevalent among rheumatoid arthritis patients and must be taken into account regardless of the degree that the disease has progressed, because the severity of the dryness is not dependent on disease progression. Additionally, a discrepancy exists between the patients' subjective sensation of their eye condition and the objective findings of the study.

Harefuah. 2011 Sep;150(9):713-8, 751.
Markovitz E, Perry ZH, Tsumi E, Abu-Shakra M.
Source
Department of Ophthalmology, Shaare-Zedek Medical Center, Ben-Gurion.

Abstract: Systemic drugs and dry eye

2011-10-26T10:19:00.000-07:00

Non-hormonal Systemic Medications and Dry Eye.

Many drugs used for chronic illnesses can contribute to dry eye syndrome, and elderly patients who have dry eye may concurrently be on systemic medications that worsen the condition. Such medications include anticholinergic drugs, eg, antidepressant, antipsychotic, anti-Parkinson's disease, and antihistamine drugs. Other drugs such as anti-acne preparations and antihypertensives can also cause dry eye. In some cases, the adverse effects of the drug on dry eye is dose-related and can be relieved by reducing the dosage. Alternatively, a different drug within the same drug family may alleviate the dry eye problem. Awareness of the drugs that contribute to dry eye will allow ophthalmologists and other physicians to better manage patients who have this common problem.

Ocul Surf. 2011 Oct;9(4):212-26.
Wong J, Lan W, Ong LM, Tong L.
Source
From the Department of Ophthalmology, Tan Tock Seng Hospital.

Abstract: Osmolality and tear film dynamics

2011-10-26T10:04:00.000-07:00

Osmolality and tear film dynamics.

The tear film is a nourishing, lubricating and protecting layer that bathes the ocular surface. It is continuously replenished through cycles of production and elimination via evaporation, absorption and drainage. These processes are often referred to as tear film dynamics. Osmolality is an objective clinical measurement that provides insight into the balance of these complex tear film dynamics. Balanced tear production and elimination is vital for tear film integrity, stability and normal osmolality. Imbalances cause alterations of the tear film structure and composition, ultimately leading to tear film instability and measurable tear film hyperosmolality. Elevated tear film osmolality is considered a core mechanism in dry eye, forming the basis of dry eye symptoms and leading to ocular surface damage. Despite its immense potential in the diagnosis of dry eye, tear film osmolality is not commonly assessed. This review will focus on the current knowledge of tear film dynamics and tear film osmolality.

Clin Exp Optom. 2011 Oct 25. doi: 10.1111/j.1444-0938.2011.00634.x. [Epub ahead of print]
Stahl U, Willcox M, Stapleton F.
Source
Vision Cooperative Research Centre, Sydney, Australia School of Optometry and Vision Sciences, University of New South Wales, Sydney, Australia Institute for Eye Research, Sydney, Australia. E-mail: u.stahl@unsw.edu.au.

Abstract: Looking at MGs of GvHD patients with a confocal

2011-10-26T09:27:00.000-07:00

Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy.

PURPOSE:
To evaluate the morphological changes of the meibomian glands (MGs) using in vivo laser confocal microscopy (CM) in dry eye (DE) patients with chronic graft-versus-host disease (cGVHD).

METHODS:
Seventeen eyes from 9 patients with a diagnosis of DE associated with cGVHD (DE/cGVHD group; 6 males, 3 females; median 50.5 years) and 16 eyes of 8 hematopoietic stem cell transplantation (HSCT) recipients without DE (non-DE/non-cGVHD group; 5 males, 3 females; median 47.0 years) were enrolled. CM was used to investigate the MG and MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), and the fibrosis grade. Clinical findings of the lid margin were obtained. Tear dynamics, ocular surface vital staining, meibography, and MG expressibility were also examined. Data were compared between the 2 groups using the unpaired t and Mann-Whitney tests.

RESULTS:
The mean MGAUD value was significantly lower in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.01, 57.8±38.3 glands/mm(2), 88.8±26.6 glands/mm(2), respectively), and the mean MGALD and MGASD were significantly shorter in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.0018, 37.3±24.4 μm and 60.4±11.8 μm, p=0.0106, 17.7±11.8 μm and 26.6±6.03 μm, respectively). The mean fibrosis grade was significantly higher in the DE/cGVHD group than the non-DE/non-cGVHD group (p<0.0001, 1.39±0.71 grade, 0.06±0.25 grade, respectively). Clinical findings in the lid margin, tear dynamics, and ocular surface findings were significantly worse in the DE/cGVHD group than in the non-DE/non-cGVHD group.

CONCLUSIONS:
CM clearly depicted the morphological changes of the MG in the DE/cGVHD group, and revealed the severity of the meibomian gland dysfunction. Patients with severe DE after HSCT showed atrophic MG and excessive fibrosis.

Mol Vis. 2011;17:2533-43. Epub 2011 Sep 29.
Ban Y, Ogawa Y, Ibrahim OM, Tatematsu Y, Kamoi M, Uchino M, Yaguchi S, Dogru M, Tsubota K.

Abstract: The use of punctal plugs in children

2011-10-26T09:21:00.000-07:00

The use of punctal plugs in children.

Background/aims
To evaluate the safety and efficacy of punctal plugs in children with dry eye syndrome.

Methods
A retrospective case series of patients who had an insertion of silicone punctal plugs for dry eye syndrome. Data collected included presenting symptoms, signs, systemic disorders if present, type of anaesthesia and complications by the time of last follow-up.

Results
Twenty-five patients (median age at insertion 7 years, range 1.5-13.8 years) were identified. Median follow-up was 18 months. The commonest symptoms were photophobia, soreness and blepharospasm, and the commonest sign was punctate epithelial erosions. Concurrent systemic disease was present in 18/25 patients. Repeated procedures were carried out in eight of 25 patients. Twenty-four of 35 insertions were performed under general anaesthesia. A substantial improvement in ocular surface disease was noted in all cases: frequency of lubricant use was reduced in eight of 25 and visual acuity improved in 15/25 patients. Spontaneous extrusion was the commonest complication and occurred within 6 months in 19% of cases.

Conclusion
Dry eye syndrome in children is often accompanied by systemic disease, so in a child with persistent symptoms this should be explored. Punctal plugs offer a safe and effective form of treatment especially as compliance of frequent lubrication is limited in children.

Br J Ophthalmol. 2011 Oct 22. [Epub ahead of print]
Mataftsi A, Subbu RG, Jones S, Nischal KK.
Source
Great Ormond St Hospital for Children, London, UK.

Abstract: Plasma rich in growth factors

2011-10-24T09:50:00.000-07:00

Important topic... have been hearing from more patients recently pursuing these alternatives to classic autologous serum.

Efficacy of Plasma Rich in Growth Factors for the Treatment of Dry Eye.

PURPOSE:
To evaluate the efficacy of plasma rich in growth factors (PRGF) for the treatment of moderate/severe dry eye.

METHODS:
PRGF treatment was administered to 16 patients who had moderate/severe dry eye diagnosed and who had not responded previously to other standard treatments. We quantified several growth factors present in the PRGF of each patient and obtained quantitative registers of the symptoms (modified score dry eye questionnaire), both before and after PRGF treatment. We also performed impression cytology to determine the degree of squamous metaplasia before and after PRGF treatment.

RESULTS:
PRGF treatment was associated with a statistically significant improvement in score dry eye questionnaire values (P < 0.001). Results from impression cytology corroborated this improvement, but the reduction in the degree of squamous metaplasia was not statistically significant. In 75% of patients treated with PRGF, no further treatments were required, whereas in the remaining 25% other ocular treatments could be reduced.

CONCLUSIONS:
PRGF led to symptom improvement in patients with moderate/severe dry eye. Surprisingly, the symptoms recorded in the dry eye questionnaire do not always agree with the degree of squamous metaplasia measured by impression cytology.

Cornea. 2011 Oct 15. [Epub ahead of print]
López-Plandolit S, Dsci MC, Freire V, Grau AE, Durán JA.
Source
From the Instituto Clínico-Quirúrgico de Oftalmología, Bilbao, Vizcaya, Spain.

Abstract: Topical Epigallocatechin Gallate (from green tea)

2011-10-17T09:02:00.000-07:00

This is early stage mice research so don't get excited yet. Interesting stuff, though, & seems to have been studied extensively in the role of skin cancer prevention. In this study it reduced clinical signs and inflammation.

Therapeutic Efficacy of Topical Epigallocatechin Gallate in Murine Dry Eye.

OBJECTIVE:
To study the efficacy of topical epigallocatechin gallate (EGCG) for the treatment of dry eye disease (DED).

METHODS:
Seven- to 8-week-old female C57BL/6 mice were housed in the controlled environment chamber to induce DED. Topical 0.01% or 0.1% EGCG, or vehicle, was applied to the eyes of DED mice. Corneal fluorescein staining and the number of corneal CD11b+ cells were assessed in the different groups. Expression of interleukin-1β, tumor necrosis factor-α, chemokine ligand 2, and vascular endothelial growth factor (VEGF)-A/C/D was evaluated by real-time polymerase chain reaction in the corneas at day 9. Corneas were stained for lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 to evaluate lymphangiogenesis, and the terminal transferase dUTP nick end labeling (TUNEL) assay was used to evaluate apoptosis of corneal epithelial cells.

RESULTS:
Treatment with 0.1% EGCG showed a significant decrease in corneal fluorescein staining compared with the vehicle (24.6%, P = 0.001) and untreated controls (41.9%, P < 0.001). A significant decrease in the number of CD11b+ cells was observed in 0.1% EGCG-treated eyes, compared with the vehicle in the peripheral (23.3%, P = 0.001) and central (26.1%, P = 0.009) corneas. Treatment with 0.1% EGCG was associated with a significant decrease in the corneal expression of interleukin-1β (P = 0.029) and chemokine ligand 2 (P = 0.001) compared with the vehicle and in VEGF-A and VEGF-D levels compared with the untreated group (P = 0.007 and P = 0.048, respectively). EGCG 0.01% also showed a decrease in inflammation at the molecular level but no significant changes in the clinical signs of DED. No cellular toxicity to the corneal epithelium was observed with 0.01% or 0.1% EGCG.

CONCLUSIONS:
Topical EGCG treatment is able to reduce the clinical signs and inflammatory changes in DED by suppressing the inflammatory cytokine expression and infiltration of CD11b+ cells in the cornea.

Cornea. 2011 Oct 11. [Epub ahead of print]
Lee HS, Chauhan SK, Okanobo A, Nallasamy N, Dana R.
Source
From the Schepens Eye Research Institute, and Massachusetts Eye and Ear Infirmary; and Department of Ophthalmology, Harvard Medical School, Boston, MA.

NC center first to offer Lipiflow

2011-10-17T08:48:00.000-07:00

I have really mixed feelings about Lipiflow. I love seeing the new innovations springing and at the same time I always seem to find myself gritting my teeth.

More effective than other methods? Probably.
How many patients cannot get sufficient improvement to MGD with other treatments? Dunno.
Pricing? Absolutely scary.
How much symptomatic relief and for how long? Probably all over the map based on what I've heard so far.

If they can make it work financially while using it on people who actually truly need it, great. One of my worries about this sort of thing is that the high-dollar treatments for the most part attract the desperate people who often have quite complex cases whose symptoms are probably not exclusively attributable to blocked MGs.

TearScience Announces First U.S.-Based Eye Care Practice, Carolina Vision Center, to Offer LipiFlow(R) Treatment

MORRISVILLE, N.C., Oct 14, 2011 (BUSINESS WIRE) -- TearScience, Inc., a privately-held medical device company, today announced that Fayetteville, North Carolina-based Carolina Vision Center, is the first eye care center in United States to commercially offer the LipiFlow(R) Thermal Pulsation System, a breakthrough treatment for evaporative dry eye disease. TearScience's LipiFlow is designed to address meibomian gland dysfunction, allowing for the treatment of eyelid gland blockages during a non-invasive procedure administered at an eye care office. Opening the blocked eyelid glands allows the glands to resume the natural production of lipids (oils) needed for a healthy tear film. TearScience received U.S. FDA clearance for its LipiFlow(R) medical device on June 28, 2011.

Abstract: Dry eye symptoms for glaucoma patients

2011-10-17T08:39:00.000-07:00

Symptoms and signs of tear film dysfunction in glaucomatous patients.

PURPOSE:
The purposes of this study were to evaluate the presence of symptoms of tear film dysfunction by using the Ocular Surface Disease Index (OSDI) questionnaire in glaucomatous patients and to examine whether they have ocular surface signs.

METHODS:
Fifty patients with ocular hypertension or open-angle glaucoma were sequentially examined. All patients used preserved antiglaucomatous drops once, twice, 3 times, or 4 times a day. Each patient filled out an OSDI questionnaire. Fluorescein corneal staining, lissamine green conjunctival staining, break-up time, and Schirmer I test were performed in patients with positive OSDI.

RESULTS:
Using the OSDI, 26 of 50 patients (52%) showed at least mild symptoms of tear film dysfunction (score >12); of them, 17 (34%) had severe OSDI (Score >32). Decrease in tear production was seen in only 8 glaucomatous patients. The break-up time was <7 s in 18 patients. Lissamine green conjunctival staining was positive in at least one eye of all the 26 patients, whereas fluorescein corneal staining was positive in at least one eye of 22 patients. A statistically significant (P<0.05) difference was found for lissamine green conjunctival staining between 16 patients using ipotensive drops once or twice a day and 10 patients using drops 3 or 4 times a day. In the group of patients using only β-blocker agents, we found a positive correlation between symptoms and vital staining of the ocular surface.

CONCLUSION:
Fifty-two percent of patients in therapy with preserved antiglaucomatous drops showed symptoms of tear film dysfunction. Signs of ocular surface diseases seemed to be greater in patients under >2 medications. Symptoms correlated to signs only in patients in monotherapy with β-blockers drops.

J Ocul Pharmacol Ther. 2011 Jun;27(3):281-5. Epub 2011 May 10.
Valente C, Iester M, Corsi E, Rolando M.
Source
Clinica Oculistica, Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, Genoa, Italy. valente81@gmail.com

Drug news: Ista's Remura

2011-10-14T09:45:00.000-07:00

Remura East was a washout... what a shame, but at least maybe we'll get yet another OTC out of it.

ISTA Pharmaceuticals Reports Results From the Second of Two Studies in the REMURA(TM) Phase 3 Clinical Program for Dry Eye Disease

IRVINE, CA, Oct 13, 2011 (MARKETWIRE via COMTEX) -- ISTA Pharmaceuticals, Inc. ISTA -1.96% today announced top-line results from the second of its two Phase 3 studies to evaluate the short-term safety and efficacy of two concentrations of REMURA(TM) (bromfenac ophthalmic solution for dry eye) in alleviating the signs and symptoms of dry eye disease. In the EAST study, REMURA was highly effective in treating a sign and symptom of dry eye but was not statistically significantly better than placebo in the entire patient cohort, a common outcome reported in studies testing other dry eye therapies. In both Phase 3 studies, safety data demonstrated REMURA was well-tolerated, with an adverse event profile similar to placebo and consistent with those observed previously with REMURA in a Phase 2 study and with other prescription dry eye drops. All three formulations were rated by patients as very comfortable.

"For the EAST study, we amended the statistical plan to focus on the subpopulation identified in the WEST study as responders. In the previously announced WEST study, the results showed a statistically significant improvement over placebo in the sign of conjunctival staining, as measured using the Lissamine Green (LG) Staining test, among female patients 51-70 years of age with moderate dry eye disease. However, the EAST study did not show a significant difference from placebo in this subpopulation, which we believe is partly due to the fact that the EAST study enrolled far fewer patients with mild to moderate dry eye disease," stated Timothy R. McNamara, Pharm.D., Vice President of Clinical Research and Medical Affairs of ISTA Pharmaceuticals. "We will complete a full analysis of the data, but focus our efforts on the potential use of the vehicle as an over-the-counter artificial tear product."

UK optometry community exhorted to do better in dry eye

2011-10-13T11:34:00.000-07:00

I appreciated seeing this little tidbit in opticianonline.net... hopefully more UK optometrists will jump in the bandwagon and embrace dry eye.

OOs urged to update eyelid hygiene advice

Optometrists are doing 'more harm than good' by advising patients to employ home-made treatments such as baby shampoo or bicarb scrubs for lid and lash conditions.

Delegates to Johnson & Johnson's White, Bright and Healthy roadshow heard that OOs should get more involved in the management of dry eye and prescribing therapeutics.

Independent West Country OO Sarah Farrant said eye care professionals should take the initiative. In her presentation on investigation and management of dry eye she said up to 30 per cent of over-50s and half of contact lens wearers would suffer from the condition but: 'GPs can't, and ophthalmologists won't', identify and treat it.

Farrant added that some practices were doing more harm than good by advising patients to use baby shampoo or bicarbonate of soda to wipe lids and lashes. 'Baby shampoo is about as disruptive to the lipid as you can get.' She also cautioned against the use of bicarb describing it as: 'the lesser of two evils'.

OO Peter Frampton, who practises in the North East, said OOs had the equipment and the skills to identify the causes of red eye in practice. He urged delegates to get trained and become prescribers of ocular therapeutic drugs. OOs have the skills to make a difference to patients with red eye and becoming a prescriber would add an extra dimension to their practice and allow them to treat patients without having to constantly refer. 'We have got to do it ourselves or we will be waiting for ever,' he added.

The roadshow also looked at contact lens complications, patient retention and diet and supplementation. They continue in Bristol, November 8 and Manchester, November 10.

Orange County dry eye support group...

2011-10-13T11:17:00.001-07:00

The OC support group now has a website! You can always check there for upcoming meeting dates. The next is Friday, november 4.

Abstract: Serum plus SiHy lens for PED

2011-10-11T09:28:00.000-07:00

Combined Application of Autologous Serum Eye Drops and Silicone Hydrogel Lenses for the Treatment of Persistent Epithelial Defects.

PURPOSE:
We investigated the utility of a combination of autologous serum eye drops and a silicone-hydrogel (SH) lens in the treatment of persistent epithelial defects (PEDs).

METHODS:
Eight patients who had distinct PED conditions were treated with 50% (v/v) autologous serum eye drops in combination with silicone hydrogel contact lenses and prospectively observed.

RESULTS:
The pathogenesis of PEDs included Sjo″gren-type dry eye syndrome, graft-versus-host disease, toxic keratitis, limbal cell deficiency, superior limbic keratoconjunctivitis, and neurotrophic keratitis. The patients had PEDs for 90±81.76 days (range: 30-240 days). Before the initiation of the combined treatment, three patients had already been unsuccessfully treated with SH lenses, and five patients had received serum eye drops alone. The PEDs of the eight eyes healed after a treatment period of 11.8±4.9 days. No visible deposits were noted on the surface of any contact lens.

CONCLUSIONS:
These findings demonstrate that the combination of an SH lens and serum eye drops may be effective in the treatment of intractable PEDs.

Eye Contact Lens. 2011 Oct 6. [Epub ahead of print]
Choi JA, Chung SH.
Source
From the Department of Ophthalmology and Visual Science (J.C.), College of Medicine, The Catholic University of Korea, St. Vincent's Hospital, Suwon, Korea; and Seoul St. Mary's Hospital (S.-H.C.), Seoul, Korea.

Abstract: Comparison of 3 lubricant eye drops

2011-10-11T09:22:00.000-07:00

Never heard of Blu Sal and Carnidrop (what country are those things sold in? any comparable drop here?) which makes the study much less interesting. So what I really want to know is... why the heck are these dry eye patients being given BAK containing lubricant drops?

Comparison of Three Lubricant Eye Drop Solutions in Dry Eye Patients.

PURPOSE.:
Lubricant eye drops that restore physiological osmolarity represent a promising strategy for dry eye syndrome as hyperosmolarity plays a central role in this disease. This preliminary study compared three lubricant eye drop solutions with different osmolarities and compositions in subjects with this condition.

METHODS.:
Subjects with dry eye syndrome undergoing treatment with benzalkonium chloride-containing lubricant eye drops were randomized to Carnidrop (n = 9), Optive (n = 9), or Blu Sal (n = 9). Fluorescein break-up time (FBUT) and Ocular Protection Index (OPI) were measured at baseline, 15 min, and 60 min after instillation to evaluate the stability and quality of the tear film.

RESULTS.:
At 15 min, a significant increase in FBUT vs. baseline was reported with Carnidrop (from 2.0 ± 0.8 to 4.8 ± 2.0; p = 0.004) but not in patients who received Optive or Blu Sal. At 60 min, FBUT was significantly increased vs. baseline with Carnidrop (from 2.0 ± 0.8 to 6.0 ± 2.8, p = 0.001) and Optive (from 2.9 ± 2.8 to 4.3 ± 2.9, p = 0.004) but not with Blu Sal. At 15 min, OPI was significantly increased from baseline in only the Carnidrop group (from 0.4 ± 0.2 to 1.0 ± 0.4, p = 0.003). This increase was significantly greater with Carnidrop than with Blu Sal (p = 0.003). At the 60 min evaluation, OPI remained significantly increased from baseline in only the Carnidrop group (p = 0.003).

CONCLUSIONS.:
Carnidrop produces a larger increase in FBUT and OPI than Optive and Blu Sal in subjects with dry eye syndrome over a 1 h period, possibly because of its hypo-osmolarity and high osmolyte (in particular l-carnitine) content. The instillation of compounds that improve the quality and stability of the tear film, which are impaired in dry eye syndrome, could be effective in the treatment of this condition.

Optom Vis Sci. 2011 Oct 6. [Epub ahead of print]
Evangelista M, Pescosolido N, Koverech A, Messano M.
Source
*MD †PhD ‡MSc Department of Aging Science (NP) and Department of Ophthalmology (ME), Faculty of Medicine and Surgery, University of Rome "Sapienza," Rome, Italy, and Sigma Tau Industrie Farmaceutiche Riunite S.P.A, Rome, Italy (AK, MM).

Abstract: Punctal and canalicular anatomy

2011-10-11T09:12:00.000-07:00

For savvy patients out there who struggle to find effective complete occlusion (plugged, replugged, cauterized, re-cauterized?) this study is rather interesting:

Punctal and Canalicular Anatomy: Implications for Canalicular Occlusion in Severe Dry Eye.

PURPOSE:
To characterize the microscopic anatomy of the lacrimal punctum and canaliculi in relation to the tarsal plate, muscle of Riolan, and Horner muscle; and to report a novel technique to excise the horizontal canaliculus in severe dry eye patients.

DESIGN:
Observational anatomic study and a retrospective case series.

METHODS:
The microscopic anatomy was studied in 86 eyelids of 25 cadavers (age range: 45-96 years, mean: 79.5 years). Surgery was performed on 18 canaliculi of 7 patients with dry eyes (age range: 37-69 years, mean: 59.9 years). In the microscopic study, 32 eyelids were incised sagittally, 38 eyelids were incised horizontally (1 mm from the eyelid margin), and 16 eyelids were incised parallel to the tarsal plate. All specimens were stained with Masson trichrome. In the surgical group, probe-guided horizontal canalicular excision with incision of the Horner muscle to the lateral edge of the lacrimal caruncle was performed. Both canalicular stumps were cauterized.

RESULTS:
In the microscopic anatomic study, the punctum and the vertical canaliculus were part of the tarsal plate with the muscle of Riolan, whereas the horizontal canaliculus was surrounded by the Horner muscle. In the surgical group, all the operated canaliculi were completely occluded without recanalization 12 months postoperatively. No complications were recorded.

CONCLUSIONS:
Based on microscopic anatomic findings that the lacrimal punctum and the vertical canaliculus are part of the tarsal plate, and that the horizontal canaliculus is surrounded by the Horner muscle, excision of the horizontal canaliculus may be an effective technique to treat patients with severe dry eyes.

Am J Ophthalmol. 2011 Oct 6. [Epub ahead of print]
Kakizaki H, Takahashi Y, Iwaki M, Nakano T, Asamoto K, Ikeda H, Goto E, Selva D, Leibovitch I.
Source
Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi, Japan.

Those scary Halloween contacts

2011-10-11T08:52:00.000-07:00

Talk about a way to have really scary eyes. Corneal melt, anyone?

Oddly enough this topic once came up on the bulletin board amidst a discussion about the high cost of scleral lenses for dry eye ("What do y'all think of those $100 scleral lenses for halloween that they sell on the web?" Eek.)

A scary look

His Halloween costume made the 15-year-old look like a horror film extra.
Only it happened days after the holiday.
After he wore a pair of novelty contact lenses to a party, the teen developed an open sore on his cornea in one eye. The infection nearly ate through his eye.
The patient was the worst that Montgomery County optometrist Dr. Geoffrey Kaplan has seen, so far, but certainly he wasn't the only one who developed problems from so-called "gray market" contact lens.
Kaplan said he sees maybe a handful of patients a year, usually around Halloween and usually teens and young adults, with the telltale signs of wearing contact lenses bought off the street. Mostly he sees patients with bacterial infections, but in some cases corneal ulcers, a vision-threatening infection.

Device news: Lipiflow gets more money

2011-10-07T13:01:00.001-07:00

For those of you waiting for Lipiflow to come to a dr. near you... with a fresh $15million going into the effort it may not be too long.

TearScience lands $15M to bring novel dry eye treatment to market

Medical device company TearScience has secured $15 million in debt financing that the company will use to support a pair of products addressing evaporative dry eye.....TearScience has U.S. Food and Drug Administration clearance on two products for dry eye. LipiView, which allows doctors to view the tear film and diagnose the condition. LipiFlow uses a combination of heat and pressure to treat it. Both diagnosis and treatment can be done in a physician’s office. LipiView was FDA-cleared in 2009. LipiFlow received FDA clearance earlier this year. The company also has marketing certification for the products in Europe.

Abstract: Functional visual acuity and tear function

2011-10-07T12:56:00.000-07:00

The relation of functional visual acuity measurement methodology to tear functions and ocular surface status.

PURPOSE:
To investigate the relation of functional visual acuity (FVA) measurements with dry eye test parameters and to compare the testing methods with and without blink suppression and anesthetic instillation.

DESIGN:
A prospective comparative case series.

METHODS:
Thirty right eyes of 30 dry eye patients and 25 right eyes of 25 normal subjects seen at Keio University School of Medicine, Department of Ophthalmology were studied. FVA testing was performed using a FVA measurement system with two different approaches, one in which measurements were made under natural blinking conditions without topical anesthesia (FVA-N) and the other in which the measurements were made under the blink suppression condition with topical anesthetic eye drops (FVA-BS). Tear function examinations, such as the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal vital staining as ocular surface evaluation, were performed.

RESULTS:
The mean logMAR FVA-N scores and logMAR Landolt visual acuity scores were significantly lower in the dry eye subjects than in the healthy controls (p < 0.05), while there were no statistical differences between the logMAR FVA-BS scores of the dry eye subjects and those of the healthy controls. There was a significant correlation between the logMAR Landolt visual acuities and the logMAR FVA-N and logMAR FVA-BS scores. The FVA-N scores correlated significantly with tear quantities, tear stability and, especially, the ocular surface vital staining scores.

CONCLUSIONS:
FVA measurements performed under natural blinking significantly reflected the tear functions and ocular surface status of the eye and would appear to be a reliable method of FVA testing. FVA measurement is also an accurate predictor of dry eye status.

Jpn J Ophthalmol. 2011 Sep;55(5):451-9. Epub 2011 Jun 30.
Kaido M, Ishida R, Dogru M, Tsubota K.
Source
Department of Ophthalmology, Keio University School of Medicine, Shinanomachi 35, Shinnjuku-ku, Tokyo, Japan.

Abstract: Mucous production and cationized gelatin nanoparticles

2011-10-07T12:47:00.000-07:00

Obviously very technical topic but we don't see a lot these days about mucin secretagogues so I thought those who follow those developments might like to see this one.

Expression of MUC5AC in Ocular Surface Epithelial Cells Using Cationized Gelatin Nanoparticles.

Decreased production of the mucin MUC5AC in the eye is related to several pathological conditions, including dry eye syndrome. A specific strategy for increasing the ocular levels of MUC5AC is not yet available. Using a plasmid specially designed to encode human MUC5AC, we evaluated the ability of hybrid cationized gelatin nanoparticles (NPs) containing polyanions (chondroitin sulfate or dextran sulfate) to transfect ocular epithelial cells. NPs were developed using the ionic gelation technique and characterized by a small size (< 200 nm), positive zeta potential (+20/+30 mV), and high plasmid association efficiency ( >95%). MUC5AC mRNA and protein were detected in conjunctival cells after in vitro transfection of the NPs. The in vivo administration of the NPs resulted in significantly higher MUC5AC expression in the conjunctiva compared to untreated control and naked plasmid. These results provide a proof-of-concept that these NPs are effective vehicles for gene therapy and candidates for restoring the MUC5AC concentration in the ocular surface.

Mol Pharm. 2011 Oct 3;8(5):1783-8. Epub 2011 Aug 2.
Konat Zorzi G, Contreras-Ruiz L, Párraga JE, López-García A, Romero Bello R, Diebold Y, Seijo B, Sánchez A.
Source
Department of Pharmacy & Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela , Campus Sur, 15782, Spain.

Abstract: Tears Again Hydrate (with and without Restasis)

2011-10-05T12:32:00.000-07:00

This is rather an interesting study and since the full text is available free you can easily review the details. They compared a group who took Tears Again Hydrate (flaxseed and evening primrose oil supplement sold on prescription) for six months with a group who took that AND took Restasis for the last 3 months of the 6 month period. In this study it didn't appear that Restasis added much.

Efficacy of a new prescription-only medical food supplement in alleviating signs and symptoms of dry eye, with or without concomitant cyclosporine A.

PURPOSE:
To evaluate the effect of a new, prescription-only medical food supplement containing omega-3 and omega-6 essential fatty acids on dry eye signs and symptoms, with or without concomitant topical cyclosporine.

METHODS:
A total of 43 subjects were randomized and followed for 6 months. Group 1 (n = 23) was assigned to take two soft geltabs of the medical food supplement by mouth twice daily for 6 months. Group 2 (n = 20) was directed to take the medical food supplement in the same manner, along with topical cyclosporine, instilled twice daily during the last 3 months of the study. Subjects were evaluated at baseline, month 1, month 3, and month 6. Primary outcome measures included tear breakup time (TBUT), conjunctival staining, corneal staining, and change in subjective symptoms.

RESULTS:
Both groups had a statistically significant improvement in TBUT between baseline and month 6. In the food supplement only group, TBUT improved by 0.805 seconds from baseline to month 6. In the supplement/cyclosporine group, TBUT improved by 1.007 seconds from baseline. There was no statistically significant difference in TBUT between the two groups at baseline, month 3, or month 6. There were no significant differences in corneal or conjunctival staining between or within groups. Subjective symptoms were also improved in both groups.

CONCLUSION:
Supplementation with the proper balance of omega-3 and omega-6 essential fatty acids improved TBUT and relieved patient symptoms. The addition of topical cyclosporine did not convey any statistically significant improvement in TBUT beyond that achieved by the supplement.

Clin Ophthalmol. 2011;5:1201-6. Epub 2011 Aug 25.
Jackson MA, Burrell K, Gaddie IB, Richardson SD.
Source
Jacksoneye, Lake Villa, IL, USA.

Abstract: Inflammatory process or no?

2011-10-03T09:25:00.000-07:00

This is an interesting study in IOVS looking at inflammatory cytokines in "pure" lipid-deficient dry eye versus aqueous deficient or combo. Their conclusion was that based on the minimal protein quantities in the "pure" lipid deficient cases (i.e. no aqueous deficiency), the disease process is not based on inflammation.

Proinflammatory Cytokine Profiling of Tears from Dry Eye Patients by Means of Antibody Microarrays.

Purpose. In the pathogenesis of keratoconjunctivitis sicca, immune processes are thought to play an important role. However, the exact details of the pathomechanisms are still unknown. In this study, the expression patterns of proinflammatory cytokines in the tears of patients with different subtypes of dry eye were analyzed. Methods.One hundred forty-three subjects subdivided into healthy controls (CTRL, n = 38), patients with aqueous-deficient dry eye (DRYaq, n = 35), patients with changes of the lipid layer (DRYlip, n = 36), and patients with a combination of both (DRYaplip, n = 34) were examined. Expression patterns of proteins (e.g., IL-1β, IL-6, ITNF-α, and IFN-γ) were examined using an advanced antibody microarray approach. Results. Several highly significant differences in the cytokine levels of dry eye patients compared with healthy controls were detected. Patients with DRYaq or those with DRYaplip showed elevated levels for most of the tested proteins. For example, IL-1β was found to be elevated 2.4-fold in DRYaq patients and 2.75-fold in DRYaqlip patients (both P < 8.00E-6). The detected amounts of protein in DRYlip patients and in healthy controls showed only minimal differences (fold increase/decrease for all proteins >1.2; P > 5.00E-1). Conclusions. The similarity between the profiles of healthy controls and DRYlip patients justifies the assumption that the pathomechanism of this dry eye subtype is based on mechanisms other than inflammation, whereas it seems to be the case for DRYaq patients.

FROM:Invest Ophthalmol Vis Sci. 2011 Sep 29;52(10):7725-7730. Print 2011.Boehm N, Riechardt AI, Wiegand M, Pfeiffer N, Grus FH.SourceExperimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Abstract: Dry eye and juvenile rheumatoid arthritis

2011-10-03T07:14:00.000-07:00

Relation of dry eye to disease activity in juvenile rheumatoid arthritis.

Purpose.

To study the frequency and severity of dry eye in patients with juvenile rheumatoid arthritis (JRA) and its relation to disease activity.

Patients and Methods.

Evaluation for dry eye was done in 40 patients with juvenile rheumatoid arthritis referred for ocular assessment in the Ophthalmology Clinics, Faculty of Medicine, Ain Shams University. They were 28 girls and 12 boys with age range of 7-12 years. Medical history, clinical examination, and full ophthalmologic evaluation were performed for each patient. The dry eye tests included tear film break-up time, Schirmer-1 test, and corneal fluorescein staining. Dry eye severity grading was used. Twenty healthy, age- and sex-matched children were assessed for dry eye as a control group.

Results.

Thirty patients (75%) showed findings consistent with the diagnosis of dry eye. Twenty patients (50%) showed first-degree dryness, 8 (20%) showed second-degree, and 2 (5%) showed third-degree. The score of dry eye severity was significantly lower in remission compared to disease activity. Multiregression analysis showed the only factor affecting dry eye parameters was the duration of illness.

Conclusions.

Dry eye is a common incident in children with JRA and should be screened for in all patients with this disease. Severity of eye dryness is highly correlated with the disease activity.

Eur J Ophthalmol. 2011 Sep 7. pii: FD250C68-C164-4BCA-8ECD-0F12DCE1E97D. doi: 10.5301/ejo.5000042. [Epub ahead of print]El-Shazly AA, Mohamed AA.SourceDepartment of Ophthalmology, Faculty of Medicine, Ain Shams University, Cairo - Egypt.

Abstract: Acupuncture for dry eye, rabbit model

2011-09-30T09:13:00.000-07:00

Interesting. I know plenty of people who have had acupuncture for dry eye, with mixed results. I have known some who found it very beneficial, though more often what I'm hearing is that people are finding it good for stress and perhaps improving coping with dry eye through the reduction of stress. If you're interested in this topic, check out acupuncture on DryEyeTalk. Here's an example of a recent discussion.

Efficacy of Acupuncture and Identification of Tear Protein Expression Changes Using iTRAQ Quantitative Proteomics in Rabbits.

Purpose:
To evaluate the effect of acupuncture on rabbit tear secretion and compare the difference in tear protein expression caused by acupuncture.

Materials and Methods:
Ten male New Zealand White rabbits were enrolled in this study. The following acupoints around the left eye, Extra 1 (Taiyang), BL 2 (Zanzhu) and SJ 23 (Sizhukong), were selected for acupuncture therapy. Each rabbit received 10 acupuncture sessions of 30 min, three times per week. A quantity of 50 μl rabbit tear was collected at the pre- and post-acupuncture stage in every subject, respectively. Total protein content analysis, one-dimensional gel electrophoresis and quantitative proteomics analysis (iTRAQ) were performed and the results were compared.

Results:
Generally, the tear protein expression after acupuncture was different from that before acupuncture though to some extent they were similar. The time spent collecting rabbit tear after acupuncture was shorter than that before acupuncture. The total protein content in rabbit tear pre- and post-acupuncture was 7.12 μg/μl versus 11.28 μg/μl, respectively. One-dimensional gel electrophoresis showed that tear proteins collected before acupuncture were substantially different than post-acupuncture proteins. In total, twenty-eight tear proteins were identified by iTRAQ. Associated with acupuncture were six up-regulated proteins (tear lipocalin, α-1-antiproteinase, histidine-rich glycoprotein, hemopexin, Vitamin D-binding protein, α-2-HS-glycoprotein) and five down-regulated proteins (Annexin A1, serum amyloid A-3 protein, Helicase-like transcription factor, 15 kDa protein A, protein S100-A9).

Conclusions:
The rabbit tear protein expression difference caused by acupuncture indicates that acupuncture not only stimulates lacrimal gland secretion function but also induces the quantitative change of some proteins in rabbit tear, which may support a positive effect of acupuncture in the treatment of dry eye.

Curr Eye Res. 2011 Oct;36(10):886-94.
Qiu X, Gong L, Sun X, Guo J, Chodara AM.
Source
Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University , Shanghai , China.

Abstract: Rasch analysis of OSDI

2011-09-30T09:05:00.000-07:00

OSDI is definitely a less than perfect tool, but hey, it's the best we got (if I'm wrong please email me a link to something better) for the time being. We patients must have a scientifically validated way to quantify our symptoms or doctors simply won't take our pain seriously (especially in the absence of dramatic clinical signs). - This is also a big issue in getting drugs FDA approved - how can you prove improvement to both signs and symptoms if you can't quantify symptoms reliably?

Rasch Analysis of the Ocular Surface Disease Index (OSDI).

Purpose:
The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Its reliability and validity has been investigated within the classical test theory framework and, more recently, using Rasch analysis. The purpose of the present analysis was to more completely investigate the functioning of its response category structure, the validity of its three subscales, and the unidimensionality of the latent construct it is intended to assess.

Methods:
Responses to the OSDI from 172 women participating in the Dry Eye in Postmenopause (DEiM) study who had previously been diagnosed with dry eye or reported significant ocular irritation and dryness were analyzed. Response category structure and item fit statistics were evaluated for assessment of model fit. Person separation statistics were used to examine the validity of the subscales. Unidimensionality was assessed by principle component analysis of model residuals.

Results:The recommended five-category response structure resulted in disordered response thresholds. A four category structure resulted in ordered thresholds. Item infit statistics were acceptable for all 12 items. Person separation with this category structure was adequate, with person separation index of 2.16. None of the three subscales demonstrated adequate person separation. PCA showed one other significant factor onto which the three environmental items loaded significantly.

Conclusions:All items demonstrated acceptable fit to the model after collapsing categories to order the response thresholds. The original subscales did not prove valid, and there is some evidence of multidimensionality and poor targeting.

Invest Ophthalmol Vis Sci. 2011 Sep 24. [Epub ahead of print]
Dougherty BE, Nichols JJ, Nichols KK.
Source
The Ohio State University College of Optometry, Columbus, OH.

Abstract: Corneal neuropathic pain and blepharospasm

2011-09-30T08:54:00.000-07:00

I really appreciate starting to see things in the pain journals on this topic.

Chronic (neuropathic) corneal pain and blepharospasm: Five case reports.

Pain and focal dystonias have been associated with chronic pain conditions such as complex regional pain syndrome. Corneal pain, frequently known as "dry eye", may be a neuropathic pain condition with abnormalities of the nerve plexus. Here we present 5 case histories of patients with defined corneal pain (with associated neuropathic features) and objective measures of changes in the nerve plexus and associated blepharospasm. A putative relationship between pain and blepharospasm suggests potential involvement of the basal ganglia in both these conditions.

Pain. 2011 Oct;152(10):2427-31. Epub 2011 Jul 12.
Borsook D, Rosenthal P.
Source
Center for Pain and the Brain, McLean Hospital, Massachusetts General Hospital, and Children's Hospital of Boston, Harvard Medical School, Boston, MA, USA.

Abstract: Demodex

2011-09-28T09:01:00.000-07:00

Clinical and immunological responses in ocular demodecosis.

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.

J Korean Med Sci. 2011 Sep;26(9):1231-7. Epub 2011 Sep 1.
Kim JH, Chun YS, Kim JC.
Source
Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.

Opinion: Are some of us murdering our meibomian glands?

2011-09-27T13:18:00.000-07:00

I have observed a trend over the past couple of years where for various reasons more people seem to be overdoing eyelid care in hopes of improving chronic MGD. They are applying heat packs twice or more each day; scrubbing and massaging their lids frequently; and attempting to express the glands regularly. I've even observed some of the savviest patients purchasing medical instruments intended for professionals and using them at home to express their glands.

As a longtime proponent of lid hygiene and heat treatment for MGD I have viewed this trend with increasing concern because I fear that inappropriate use, and over-use, of such treatments might delay rather than assist recovery of the meibomian glands. As I so often have over the years, I went to the doctor who first helped me understand dry eye diseases to elucidate this topic for me. What follows is an article that she wrote for DEZ readers in the wake of our discussion about whether some of us may be actually beating our meibomian glands to death. Enjoy, and please let us know what you think in comments here or via email/dryeyetalk/etc.

Expressing the meibomian glands
by Sandra M. Brown, MD - Cabarrus Eye Center, Concord NC

The meibomian glands live in the upper and lower eyelids. There are approximately 15 - 20 glands per lid. The gland openings lie on the edge of the eyelid just inside the eyelash line. The body of the gland is inside the tarsal plate, which is a very thin piece of cartilage that gives the eyelid its defined shape. When your doctor everts your lid (flips it inside out) he is flipping over the tarsal plate.

Although most diagrams of meibomian glands show a hollow tubular structure that looks like a permanently open space, a meibomian gland is more of a potential space. If the gland is empty of meibomian oils, it collapses in on itself. In fact even when the gland is "full" only a very thin film of oils may actually separate the cells lining the walls of the meibomian gland.

Meibomian oils are not squirted onto the surface of the eye. They seep out slowly under the gentle pumping action of eyelid blinking, combined with continuous oil production which pushes oils out onto the eye lid margin when the gland's potential space is fully expanded.

When the eyelid margin becomes inflamed, this inflammation can "cap off" the meibomian gland orifices. There are numerous causes of eyelid margin inflammation that will not be discussed here. If the glands continue to vigorously produce oils, the oils erupt through the sides of the glands and coalesce into a mass commonly referred to as a stye. However in many patients, obstruction of normal oil seepage causes the meibomian gland to decrease production and the oils retained in the gland become thick and degraded.

In the past 2 - 4 years, eye care providers have become more widely aware of the connection between meibomian gland dysfunction and ocular surface symptoms. One simple office test is to lightly press on the glands while the patient is seated at the slit lamp. The examiner is looking for the quantity and quality of oils, how many glands express, how hard s/he has to push to make this happen, and how readily the oils disperse into the tear film. Meibomian oils are quite easy to see at the slit lamp but essentially impossible to see with the naked eye except through elaborate magnification methods.

It is not necessary for 100% of the meibomian glands to function for adequate oils to be secreted into the tear film. Many asymptomatic patients have far fewer than 100% of the glands producing oils at any given time. Lower lid meibomian glands seem to "take a hit" sooner that upper lid glands, so it is important for your doctor to express both upper and lower lids to give your glands an overall function score. Patients with about 80% of their upper lid glands functioning well may have no symptoms even if the lower lid glands are producing almost nothing.

Eye care providers sometimes prescribe meibomian gland self-expression or patients take it upon themselves to "clear out" their glands periodically. Generally the process is to apply heat to liquefy the oils, followed by eyelash cleaning (or sometimes the reverse order) and then gland expression.

A note on hot compresses. The temperature of eyelid skin is slightly below core "body temperature" and meibomian oils become more liquid just a little above core body temperature. So moderate, sustained heat can keep viscous oils thinner. Patients who use very hot compresses that they can tolerate for only 1-2 minutes are going about it the wrong way. Washclothes are ridiculous due to the very rapid cool-down. There is no difference between dry and wet heat from the perspective of the interior of the meibomian gland. A compress that stays "definitely warm" witout being uncomfortable for at least 4 minutes is probably the most effective approach. It is impossible to really "study" the differences between compress methods.

As regards meibomian gland self-expression, there are several problems with this activity.

First, not all meibomian gland problems are due to blockage of the orifices. If the glands are simply under-producing oils (a common problem in peri-menopausal women) pushing on them won't do anything. If the lid margin inflammation is not under control and the orifices are tightly blocked, oils may not express even with hard pressure. So the treatment is not helpful. But secondly, self-expression can be harmful.

Remember that the gland is a potential space containing a small volume of oil. If you express all the oil out of the gland, you have probably expressed several days' worth of "production". You have depleted your supply. When the gland is empty, it collapses in on itself and the cells lining the potential space come into contact with each other without an intervening "oil slick". This allows the cells to adhere to each other. As the gland refills with oil the potential space expands and the cells separate. Repeated expression can lead to the cells permanently adhering, causing obstructions deeper in the gland. This process will be hastened by the microtrauma induced through the mechanical pressure, especially if applied vigorously and often.

I have seen patients who have basically murdered their meibomian glands through excessive self-expression. How do I know? Because the glands in the far nasal and temporal (ear side) areas are harder to reach. It is also more difficult to apply direct firm pressure to the glands in the upper lids than to those in the lower lids. So I see more non-functioning glands in the centers of both lids than the corners, and the lower lids have more non-functioning glands than the upper lids.

When is self-expression helpful? Some patients have mildly occluded orifices or tend to produce oils that don't seep well. They get into a "stagnation" situation. As part of their overall rehabilitation which MUST include efforts to improve oil quality and open the orifices, mild self-expression following a hot compress can be beneficial.

If you are a frequent (more than once per week) or aggressive self-expresser, ask yourself whether you are doing this "philosophically" because it seems like a smart thing to do or whether expressing truly improves your symptoms. If you are expressing several times per day, it is extraordinarily unlikely that you are getting a "useful" amount of oils onto the ocular surface each time. This habit will only increase the microtrauma to the meibomian gland structure.

Meibomian gland self-expression can be useful at certain stages of treatment. It is recommended by eye care providers, including those who specialize in ocular surface disease. It is important to understand that you can overdo it. You should not use self-expression unless instructed to do so by your eye care provider. If you have ocular surface pain and your provider has never expressed your glands, find a different doc.

What if you are a non-producer? Patients whose meibomian glands have ceased production are in a particularly difficult state. Peri- and post-menopausal women are most prone to this condition since meibomian gland function is regulated by androgen hormones. Some women become abruptly dry during pregnancy and don’t recover after pregnancy. Conversely some women have symptoms before pregnancy and actually feel better during pregnancy. We do not have a good understanding of the complex hormonal interplay that affects meibomian gland function. However, if your glands aren't making oils because they aren't receiving "go" signals from hormones or ocular surface nerves, many of the treatments described above will not be effective. Low production can combine with eyelid inflammation to further reduce the quality and quantity of oils reaching the tear film. Certainly related problems such as eyelid inflammation should be addressed. But for patients whose essential problem is markedly reduced production, it is particularly important to leave your meibomian glands alone!

Remember that the purpose of meibomian gland oils is to stabilize the tear film structure and slow evaporation. Barrier methods to slow evaporation (goggles, masks, etc.) are particularly helpful in this circumstance.

What helps meibomian glands and how:

heat - liquifies oils which tend to become more viscous just below body temperature (eyelid skin cooler than core body temp); see comments above about correct hot compress

doxycycline and minocycline, erythromycin - low dose for at least 60 days - acts as an anti-inflammatory which opens the orifices, thins out the oils in some fashion that we don't understand, decreases the bacterial load on the eye lid margins which opens the orifices

TobraDex ointment - anti-inflammatory, decreased bacterial load; intraocular pressure must be followed if used for more than 1 month

Restasis - in my experience anti-inflammatory effects can improve meibomian gland inflammation as well

omega oils - antiinflammatory, antioxidant, 'good ingredient' for oil production

Azasite applied to eye lid margins (topical equivalent of erythromycin) - antibacterial, maybe something else as well? seems to work for some people not others

Abstract: Ocular surface disease treatment algorithm

2011-09-26T07:00:00.000-07:00

This is a nice summary of steps involved in treating dry eye.

A practical treatment algorithm for managing ocular surface and tear disorders.

Management of ocular surface irritation and morbidity associated with dry eye has been plagued by the complex interplay of different pathogenic elements and substantial variability of ocular surface deficits in patients. A practical algorithm is proposed to achieve effective management of dry eye. When the eye is open, ocular surface health is governed by a stable tear film that is maintained by neuroanatomic integration via 2 reflexes. Any dysfunctional element in this neuroanatomic integration is potentially pathogenic and creates ocular surface deficits leading to dry eye. In general practice, 5 major dysfunctional elements have been identified: decreased ocular surface sensitivity, aqueous tear deficiency, lipid tear deficiency, delayed tear clearance, and ineffective tear spread. Clinical workup should be individualized to identify all such dysfunctional elements in each patient through history taking, external and slit-lamp examination, and special tests. However, practical management lies in the detection of delayed tear clearance. The following strategies are advised: (1) eliminate all intrinsic inflammatory, infectious, allergic, and toxic insults, especially those associated with delayed tear clearance; (2) correct diseases that impede and interfere with tear spread and capacity; (3) create delayed tear clearance for aqueous tear-deficient dry eye by punctual occlusion; and (4) treat lipid-deficient dry eye after sufficient aqueous tears have been conserved. The aforementioned algorithm ameliorates ocular surface irritation and curtails morbidity in most patients. This algorithm can also be adopted for complex cicatricial ocular surface diseases before managing the remaining deficits resulting from hydrodynamic deficiency.

Cornea. 2011 Oct;30 Suppl 1:S8-S14.
Tseng SC.
Source
From the Ocular Surface Center and Ocular Surface Research & Education Foundation, Miami, FL.

Drugs in development: VGX-100

2011-09-26T06:43:00.000-07:00

Early stage research but sounds interesting.

VGX-100 Identified as Potential New Therapy for Dry Eye Disease

MELBOURNE, Australia, Sept. 13, 2011 /PRNewswire via COMTEX/ -- Data published in the scientific journal Archives of Ophthalmology generated by investigators at the Schepens Eye Research Institute led by Harvard University Professor Reza Dana.

VGX-100 significantly reduced inflammation and corneal epitheliopathy in a mouse model of Dry Eye Disease.

Data indicates major potential opportunity for VGX-100 as a therapeutic for Dry Eye Disease.

Circadian Technologies Limited (asx:CIR)(otcqx:CKDXY) announced today the publication of data in the scientific journal Archives of Ophthalmology showing that its lead development molecule VGX-100, a human antibody against the angiogenic and lymphangiogenic molecule VEGF-C, can significantly reduce inflammation and corneal tissue damage associated with Dry Eye Disease (DED). The data indicates a major new therapeutic opportunity for VGX-100 in the DED setting.

The manuscript entitled "Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease" Arch Opthamol. Dol:10.1001/archopthamol.2011.266 is accessible via the Archives of Ophthalmology website ( http://archopht.ama-assn.org ).

DED is a complex, immune-mediated disorder of the ocular surface that has multiple causes and affects about 5 million Americans above the age of 50 years. It is estimated that 10% of Australians will suffer from the condition at some point in their lives. DED severely impacts the vision-related quality of life and the symptoms, including persistent dryness, burning, light sensitivity, pain and blurred vision, can be both psychologically and physically debilitating. The current therapeutic options for DED are limited and mostly palliative. Currently, topical cyclosporine-A is the only approved treatment for DED.

The study, which was led by Professor Reza Dana and Dr. Sunali Goyal of the Schepens Eye Research Institute, Harvard Medical School Department of Ophthalmology, showed that administration of VGX-100 was able to significantly reduce inflammation, lymphangiogenesis and corneal damage in a mouse model of DED.

Prof Reza Dana, MD MSc MPH. Claes Dohlman Chair in Ophthalmology, Professor of Ophthalmology, Harvard Medical School, Co-Director of Research at Schepens Eye Research Institute and senior author of the study said: "Dry Eye Disease is suffered by millions of people in the U.S., but current treatments have significant limitations, and effective treatments are not available for many patients. This current study builds on our previous findings demonstrating that VEGF-C, VEGF-D and VEGFR-3 are upregulated in DED corneas, and demonstrates for the first time that an anti-lymphatic effect, caused by the blockade of VEGF-C, has significant beneficial effects in treating the condition. We strongly believe that blocking lymphangiogenic molecules could become a major new paradigm for the treatment of DED."

Mr. Robert Klupacs, CEO of Circadian Technologies, said: "We have always believed that blockade of VEGF-C will have clinical utility in a variety of conditions, in addition to treating solid tumours. This very exciting data generated by our collaborators at Schepens offers significant opportunities for us to leverage our investment in the VGX-100 oncology program and undertake additional preclinical and clinical development activities for VGX-100 in DED, a disease which still remains extremely difficult to treat."

Support groups: Oct 6, Rochester NY, thyroid eye disease

2011-09-26T06:25:00.000-07:00

Kudos to Patricia Marino for organizing this. Should be well worth attending... James Aquavella is a superb corneaMD and will be participating.

Flaum Eye Institute Expert to Discuss Thyroid Eye Disease Oct. 6
New support group forms for people with painful ophthalmic condition

A new support group for people with thyroid eye disease – a painful condition resulting from Graves’ disease – will meet at 5:30 p.m. Thursday, Oct. 6, at the Flaum Eye Institute at the University of Rochester Medical Center, 210 Crittenden Blvd. James Aquavella, M.D., cornea surgeon with the Eye Institute, will discuss dry eye related to the disorder and offer tips for relief.

Thyroid eye disease is closely associated with Graves' disease, an autoimmune disorder and the leading cause of hyperthyroidism, or overproduction of the thyroid gland. The eye problems occur when cells from the immune system attack the muscles and other tissue around the eyes, causing inflammation and a build-up of muscle tissue and fat behind the eye socket. As the deposits grow, it causes the eyeballs to bulge. It’s long believed that the late actor Marty Feldman, best known for his role in “Young Frankenstein,” had thyroid eye disease.

The Rochester-area support group is open to anyone with Graves’ disease or thyroid eye disease, as well as their family members. It offers a forum to share concerns, feelings and information, and offers peer support and encouragement to patients to help them cope with their illness. Spouses and caregivers also can gain a better understanding of the disease and how to support their loved ones. Advance registration is requested. Contact Steve Kofron at (585) 275-3977.

Patricia Marino, Ph.D., an organizer of the group, will share her story of diagnosis and treatment. The retired Rochester City Schools lead teacher and specialist/coach was diagnosed Graves’ disease in 2005. Under the care of Flaum Eye Institute Director Steven Feldon, M.D., M.B.A., an international expert in thyroid eye disease research and care, Marino has overcome most of her symptoms and related challenges. She hopes to offer others helpful support and advice as they cope with the illness.

Dry eye drugs: Regenerx RGN259 completed Phase II

2011-09-24T10:47:00.000-07:00

Results expected late October.

More details in news report.

ROCKVILLE, Md., Sep 23, 2011 (BUSINESS WIRE) -- RegeneRx Biopharmaceuticals, Inc. RGRX -3.13% ("the Company" or "RegeneRx") today announced that treatment and follow-up have been completed on 69 patients in the Company's Phase 2 clinical trial with RGN-259 for the treatment of dry eye syndrome, five more than the number of evaluable patients contemplated in the trial's protocol. After all study data completes the quality control process and data lock it will then undergo statistical analyses. The trial is on schedule for top-line results to be reported in late October.

This double-masked, placebo-controlled clinical trial will evaluate the safety and efficacy of RGN-259, the Company's proprietary preservative-free eye drops, in patients with dry eye syndrome. Patients received RGN-259 or placebo twice daily for 30 days. Signs and symptoms of dry eye, such as the degree of ocular surface damage, ocular itching, burning and grittiness, among others, was graded periodically during and following the treatment period. The trial is being conducted by Ora Inc., an ophthalmic contract research organization that specializes in dry eye research and clinical trials. Additional details regarding the Phase 2 trial are available at:

http://www.clinicaltrials.gov/ct2/show/NCT01387347?term=thymosin +beta+4&rank=5

Abstract: Mucin gene expression useful in diagnosing DES

2011-09-24T07:59:00.000-07:00

I always think this area of DES research is not emphasized enough so it is nice to see this study.

OCULAR MUCIN GENE EXPRESSION LEVELS AS BIOMARKERS FOR THE DIAGNOSIS OF DRY EYE SYNDROME.

Purpose:
To evaluate mRNA levels of the ocular mucins MUC1, MUC2, MUC4, MUC5AC, and MUC7 in conjunctival impression cytology samples from patients with moderate to severe dry eye syndrome (DES) compared with a population of healthy subjects; and to investigate the use of the levels of these mucin genes as biomarkers of DES and subsequently as a potential diagnostic test for DES.

Methods:
This prospective study commenced in the year 2000 and ended in the year 2009. Thirty eight DES patients and 43 age- and gender-matched healthy subjects completed the initial part of the study. Investigations were repeated at a later stage in 16 healthy subjects and 30 DES patients, which were used as external validation data. Conjunctival impression cytology was performed in all subjects to test gene expression of ocular mucin genes MUC1, MUC2, MUC4, MUC5AC and MUC7. Statistical analysis was performed to determine if there was a difference in the levels of mucin gene expression between the two groups of subjects. Sensitivity and specificity of mucin gene expression for the diagnosis of the DES was calculated.

Results:
The expression of MUC1, MUC2, MUC4 and MUC5AC (P<0.0001) were significantly lower in conjunctival epithelium of patients with DES compared to normal subjects. These results were replicated in the external control subject and patient groups. MUC1 expression levels demonstrated the greatest sensitivity (83.3%) and specificity (87.5%) among all genes tested.

Conclusions:
Our data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials.

Invest Ophthalmol Vis Sci. 2011 Sep 19. [Epub ahead of print]
Corrales RM, Narayanan S, Fernández I, Mayo A, Galarreta DJ, Fuentes-Páez G, Chaves FJ, Herreras JM, Calonge M.
Source
CIBER-BBN (Networking Center for Biomedical Research-Biomaterials, Bioengineering, and Nanomedicine) in Valladolid; Carlos III Health Institute, Ministry of Science and Innovation, Spain.

And, uh, Twitter

2011-09-23T22:15:00.001-07:00

http://twitter.com/DryEyeZone

Facebook page

2011-09-23T22:06:00.000-07:00

I was dragged there kicking and screaming, honest...

Anyway, here's DryEyeZone on Facebook.

Drug news: SAR 1118

2011-09-21T22:48:00.001-07:00

Whoopie, we finally have an addition to the Phase III trial drugs!

SARcode Bioscience announced on Sept. 14 that enrollment is underway for a Phase 3 trial of SAR 1118 ophthalmic solution:

First Patient Enrolled in SARcode Bioscience's Pivotal Dry Eye Study of SAR 1118 Ophthalmic Solution

BRISBANE, Calif., Sept. 14, 2011 /PRNewswire via COMTEX/ -- SARcode Bioscience, Inc., a privately-held biopharmaceutical company, announced today that the initial patient has been enrolled in the company's pivotal Phase 3 clinical study (OPUS-1) of SAR 1118 ophthalmic solution.

SAR 1118 is a first-in-class molecule that inhibits T-cell inflammation by blocking the binding of two key cellular surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade. SAR 1118 may be able to reduce inflammation associated with dry eye disease.

The OPUS-1 trial will study the safety and efficacy of SAR 1118 in the treatment of dry eye disease. Approximately 588 patients will be randomized to receive SAR 1118 5.0% ophthalmic solution or placebo twice daily over 12 weeks. The co-primary endpoints of the study are corneal fluorescein staining score and visual-related function score (reading, driving at night, computer use, and watching television) as measured by the Ocular Surface Disease Index (OSDI), a validated instrument designed to assess the impact of dry eye upon vision-related activities. The safety and tolerability of SAR 1118 compared to placebo at 12 weeks will also be evaluated.

Abstract: Dry eye in Japan

2011-09-21T22:45:00.000-07:00

Prevalence and Risk Factors of Dry Eye Disease in Japan: Koumi Study.

OBJECTIVE:
To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan.

DESIGN:
Cross-sectional study.

PARTICIPANTS:
We included 3294 subjects, aged ≥40 years who were in the residential registry for Koumi town.

INTERVENTION:
Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors.

MAIN OUTCOME MEASURES:
Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors.

RESULTS:
Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.5-23.9) was higher than that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51-4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for DED in women.

CONCLUSIONS:
Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese.

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

Ophthalmology. 2011 Sep 1. [Epub ahead of print]
Uchino M, Nishiwaki Y, Michikawa T, Shirakawa K, Kuwahara E, Yamada M, Dogru M, Schaumberg DA, Kawakita T, Takebayashi T, Tsubota K.
Source
Department of Ophthalmology, School of Medicine, Keio University, Tokyo, Japan; Ryogoku Eye Clinic, Tokyo, Japan.

Abstract: Non-contact meibography

2011-09-21T22:25:00.000-07:00

I kind of like the sound of this. Anything that can truthfully claim to be predictive of dry eye symptoms has something going for it.

Non-contact meibography: Keep it simple but effective.

PURPOSE:
Meibography is reported to be important in Meibomian Gland Dysfunction (MGD) evaluation. Our purpose was to investigate the usefulness of a standard infra-red video security camera in meibography.

METHODS:
Meibographs were taken of the right lower lid of 17 subjects (female 10; age=44.3years ±13.3 SD), randomly selected from the patient pool of Horst Riede GmbH, Weinheim, Germany. Meibomian glands (MG) were photographed by an near adapted infra-red video security camera and extend of MG loss (MGL) was measured by digital image analyzes. Lipid-layer and non-invasive break-up time (NIBUT) was measured by tearscope, dry eye symptoms were evaluated by the Ocular Surface Disease Index (OSDI). Correlations between MGL scores and ocular signs, tearfilm and symptoms were analyzed by Pearsons, differences between gender by U-test. The ability of MGL to predict dry eye symptoms was evaluated by area under the receiver operative characteristic curve (AUC).

RESULTS:
MGL scores were significantly correlated to lipid-layer pattern (r=-0.68, p=0.001) NIBUT (-0.46, 0.032) OSDI (0.89, 0.001) and age (0.61, 0.005). MGL was significantly larger in female (p=0.001). AUC of MGL was 95.8% (p=0.001; sensitivity=88.9%; specificity=87.5%; threshold=32.3%).

CONCLUSIONS:
MGL is a predictive test of dry eye symptoms. The analyzed significant correlation between MGL and tearfilm and dry eye symptoms indicates the usefulness of the non-contact IR meibograph (PNCM).

Cont Lens Anterior Eye. 2011 Aug 30. [Epub ahead of print]
Pult H, Riede-Pult BH.
Source
Optometry and Vision Research, Weinheim, Germany; Contact Lens & Anterior Eye Research Unit, School of Optometry & Vision Sciences, Cardiff University, UK.

Abstract: Contacts and computers (again)

2011-09-21T22:18:00.000-07:00

Approximately one gajillion studies have been published to date showing the effects of any one or all of office air, computers and contact lenses for the ocular surface. Occasionally they're even somewhat interesting or informative.

The Impact of Contact Lens Wear and Visual Display Terminal Work on Ocular Surface and Tear Functions in Office Workers.

PURPOSE:
To evaluate the effect of contact lens (CL) wear and visual display terminal (VDT) work on the ocular surface and tear functions.

DESIGN:
Prospective case-control study.

METHODS:
Sixty-nine CL wearers (45 women and 24 men; mean age, 35.2 ± 7.3 years), and 102 age- and sex-matched non-CL wearers were enrolled in the study (66 women and 36 men; mean age, 36.7 ± 7.3 years). Ocular surface and tear function tests, including vital stainings (fluorescein and rose bengal), Schirmer test, tear meniscus height measurement, and tear film break-up time were performed. The subjective symptoms of dry eyes were evaluated using a dry eye symptom questionnaire. The participants were divided into 4 subgroups according to the total time of VDT work in 1 day (VDT work time in 1 day ≥ 4 hours or < 4 hours) and presence of CL wear. Main outcome measures included ocular surface vital staining scores, Schirmer test results, tear film break-up time, tear meniscus height measurement, and symptom questionnaire score.

RESULTS:
CL users and long-term VDT workers showed significantly worse tear meniscus height values than non-CL users and short-term VDT workers (P < .001). The mean visual symptom scores in CL wearers and long-term VDT workers were significantly higher than the other groups (P < .001).

CONCLUSIONS:
Office workers who wore CLs and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume with significant dry eye and visual symptoms triggered by environmental factors.

Am J Ophthalmol. 2011 Aug 24. [Epub ahead of print]
Kojima T, Ibrahim OM, Wakamatsu T, Tsuyama A, Ogawa J, Matsumoto Y, Dogru M, Tsubota K.
Source
Johnson & Johnson Ocular Surface and Visual Optics Department, Keio University School of Medicine, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Diagnostics: Health Canada approves InflammaDry Detector

2011-09-21T22:13:00.000-07:00

RPS Announces Health Canada Approval of RPS InflammaDry Detector™
(August 22, 2011)
Ten-minute test allows clinicians to detect inflammation in the tears of patients with Dry Eye disease

Email PDF Print
Sarasota, FL (PRWEB) August 22, 2011

On August 11, Health Canada granted Rapid Pathogen Screening, Inc. a Medical Device License for the RPS InflammaDry Detector, the first and only rapid, in-office test to detect elevated levels of MMP-9 in tear fluid. Receiving a Medical Device License allows RPS to begin marketing the RPS InflammaDry Detector in Canada, following the product’s recent release in Europe and Asia. RPS anticipates that the RPS InflammaDry Detector will soon be available for sale in Canada through a reputable distribution partner.

Clinical signs of Dry Eye aren’t always directly related to patient complaints, making this disease difficult to diagnose. Additionally, inflammation is often present in Dry Eye patients long before the appearance of clinical signs. Matrix metalloproteinase-9 (MMP-9) is an inflammatory marker that has consistently been shown to be elevated in the tears of patients with Dry Eye disease. Elevated levels of MMP-9 correlate with clinical exam findings and research shows that MMP-9 may be a more sensitive marker than clinical signs when diagnosing Dry Eye. In addition, studies show that the diagnosis and treatment of elevated levels of MMP-9 prior to LASIK surgery may result in improved wound healing and reduced complications.

The RPS InflammaDry Detector requires only a small sample of human tears to detect elevated levels of MMP-9 and provides results in just 10 minutes. Similar to the company’s first product, the presence of a single blue control line indicates a negative test result and the appearance of both a blue control line and a red result line indicate a positive result. This in-office test can be performed on patients that present with signs and symptoms of Dry Eye or as part of pre-operative screening on patients having LASIK or cataract surgery. By using the RPS InflammaDry Detector, clinicians can make an accurate diagnosis and implement an appropriate treatment plan before patients leave the office.

“Receiving a Medical Device License from Health Canada for the RPS InflammaDry Detector is yet another exciting recent accomplishment for RPS,” says Dr. Robert Sambursky, president and chief medical officer of RPS. “Providing clinicians with a rapid and accurate in-office screening test to detect hidden Dry Eye disease will help identify patients that may benefit from perioperative therapy to improve their ocular surface, leading to better surgical and medical patient outcomes.”

The RPS InflammaDry Detector has a clinical sensitivity of 85% and a specificity of 94%. This level of accuracy allows the clinician to make an appropriate diagnosis and an informed treatment decision during the initial office visit. To learn more about the RPS InflammaDry Detector or other RPS products, visit http://www.rpsdetectors.com.

Abstract: Serum drops from SJS vs other dry eye patients

2011-09-21T20:50:00.000-07:00

Interesting... in case any SJS patients were worried their blood might not be as good as the next person's for serum drops.

Stability of Epitheliotrophic Factors in Autologous Serum Eye Drops from Chronic Stevens-Johnson Syndrome Dry Eye Compared to Non-autoimmune Dry Eye.

Purpose:
To compare the concentrations of epitheliotrophic factors in autologous serum eye drops (ASE) prepared from sera of chronic Stevens-Johnson syndrome (SJS) patients with dry eyes to those prepared from non-autoimmune dry eye controls and to study the stability of the epitheliotrophic factors in different storage conditions.

Methods:
Twenty-percent ASE were prepared from 10 chronic SJS patients with dry eyes and 10 age-matched non-autoimmune dry eye controls. The concentrations of major epitheliotrophic factors comprising epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-β1), transforming growth factor-beta2 (TGF-β2), and fibronectin in those ASE preparations were determined by enzyme-linked immunosorbent assay (ELISA) at baseline and after different storage conditions: at 4°C for 1 week and 1 month; and at -20°C for 1, 3 and 6 months.

Results:
There were no significant differences in the concentrations of EGF, TGF-β1, TGF-β2 and fibronectin in 20% ASE between the SJS and control groups (EGF: 176.9 ± 40.9 vs. 185.5 ± 36.9 pg/mL, TGF-β1: 9.5 ± 2.1 vs. 9.5 ± 1.9 ng/mL, TGF-β2: 55.3 ± 30.0 vs. 63.91 ± 45.6 pg/mL and fibronectin: 70.5 ± 20.2 vs. 62.2 ± 21.3 µg/mL, respectively). These factors were stable at 4°C for up to 1 month. Storage at -20°C for up to 6 months resulted in a slight decrease in TGF-β1 (SJS: from 9.5-8.4 ng/mL, p < 0.01 and control: from 9.5-8.1 ng/mL, p < 0.01).

Conclusions:
The results suggested that the epitheliotrophic capacity of ASE from chronic SJS should be comparable to those from non-autoimmune dry eye patients, and that ASE should be sufficiently stable for up to 6 months, if stored properly at -20°C.

Curr Eye Res. 2011 Sep;36(9):775-81.
Phasukkijwatana N, Lertrit P, Liammongkolkul S, Prabhasawat P.
Source
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand.

Abstract: Modified fluorescein strip in BUT measurements

2011-09-21T20:02:00.000-07:00

A new modified fluorescein strip: Its repeatability and usefulness in tear film break-up time analysis.

PURPOSE:
To (i) analyze the repeatability of fluorescein instillation from a modified fluorescein strip (MFS) compared to a standard fluorescein strip (FS), and to (ii) observe its usefulness in the measurement of the fluorescein break-up time (FBUT) in comparison to the Tearscope (NIBUT).

METHODS:
In-vitro: Intra- and inter-observer repeatability in fluorescein instillation from the MFS and FS was evaluated by fluorescence analysis (n=10, each). In-vivo: BUT of the right eye of 20 randomly selected subjects (mean age 43.3±11.5, range=21-60 years, 8 males, 12 females) was measured by use of the Tearscope and MFS. Subjects were grouped by the Ocular Surface Disease Index (OSDI) score into 8 OSDI+ and 12 OSDI- by a cut-off value of 15.

RESULTS:
In-vitro: Intra-observer 95% limit of agreement (LoA) of the MFS was similar to the FS LoA in observer 1 (O1), but better than the FS LoA in observer (O2) (MFS: O1: LoA=±1.98mW; p=0.179; O2: ±2.71; 0.442; FS: O1: ±1.71; 0.246; O2: ±4.11; 0.512). Inter-observer LoA in fluorescence was better in MFS (±1.42; 0.111) than in FS (±3.71; 0.003). In-vivo: MFS-BUT was significantly shorter than the NIBUT (p=0.002), but significantly correlated (r=0.864, p<0.001). NIBUT and MFS-BUT were significant discriminators (p<0.001) of OSDI±(0.948/8s and 0.938/5s [AUC/cut-off value]; NIBUT and MFS-BUT, respectively).

CONCLUSIONS:
The MFS was better in the repeatability of fluorescein instillation than the FS. NIBUT and MFS-BUT were good discriminators of dry eye symptoms, but differ in their cut-off values.

Cont Lens Anterior Eye. 2011 Aug 16. [Epub ahead of print]
Pult H, Riede-Pult BH.
Source
Optometry and Vision Research, Weinheim, Germany; Contact Lens & Anterior Eye Research Unit (CLAER), School of Optometry and Vision Sciences, Cardiff University, UK.

Abstract: Oral azithromycin for posterior bleph

2011-09-21T19:57:00.000-07:00

Unimpressive results. What do we care if some fraction of our numbers improve and we still feel lousy?

Oral azithromycin for treatment of posterior blepharitis.

PURPOSE:: To evaluate the effects of oral azithromycin in patients with posterior blepharitis.

METHODS:: Twenty-six eyes of 13 patients with posterior blepharitis diagnosed by a qualified ophthalmologist were enrolled in this study. Patients were instructed to use oral azithromycin 500 mg per day for 3 days in 3 cycles with 7-day intervals. Subjective clinical outcomes were graded and scored 1 day before and 30 days after the end of the treatment (53 days after initiating the treatment) based on severity scores of: (1) eyelid debris; (2) eyelid telangiectasia; (3) swelling of the eyelid margin; (4) redness of the eyelid margin; and (5) ocular mucus secretion. For the assessment of global efficacy, patients were asked by the investigator to rate the subjective symptoms (eyelid itching, ocular itching, eyelid hyperemia, ocular hyperemia, ocular mucus secretion, photophobia, foreign body sensation, and dry eye sensation) on a scale of 0 (no symptoms) to 5 (severe symptoms). Break-up time, Schirmer I test, corneal fluorescein staining score, and rose bengal staining score were also performed in all patients.

RESULTS:: All clinical outcomes scoring showed statistically significant improvement after oral azithromycin, except for eyelid swelling. Average subjective symptom grading improved statistically after treatment with oral azithromycin, except for eyelid hyperemia, photophobia, and foreign body sensation. Average tear film break-up time values showed statistically significant improvement after the treatment with oral azithromycin. No statistically significant improvement was observed on average values of Schirmer I test, corneal fluorescein staining score, and rose bengal staining score.

CONCLUSIONS:: The combination of multiple clinical parameters shown in this study supports the clinical efficacy of pulsed oral azithromycin therapy for the management of posterior blepharitis.

Cornea. 2011 Oct;30(10):1145-9.
Igami TZ, Holzchuh R, Osaki TH, Santo RM, Kara-Jose N, Hida RY.
Source
From the *Department of Ophthalmology, Hospital das Clínicas of Universidade de São Paulo (USP), Sao Paulo, Brazil; and †Department of Ophthalmology, Santa Casa de São Paulo, Sao Paulo, Brazil.

OTC: Tears Again advanced liposome spray

2011-09-21T19:37:00.000-07:00

Based on past experience I feel like i need to add a disclaimer to this kind of post:

I am posting this NOT because I am personally recommending the product, but rather because there was a press release and there may be people among my readers (past users of liposome sprays?) who will be interested in knowing. One of my many goals with the websites and newsletter is to help people access products that are not widely known or are not available in every drugstore.

Tears Again® advanced Liposome Spray Now Available at CVS

ROSENBERG, Texas, Aug. 16, 2011 /PRNewswire/ -- OCuSOFT, Inc., an ophthalmic research, development, and supply company is pleased to announce that Tears Again® advanced Liposome Spray, an adjunct to OCuSOFT® Lid Scrub™ Eyelid Cleansers, is now available nationwide at all CVS drug stores.
Recent reports from the International Workshop on Meibomian Gland Dysfunction* (MGD) demonstrate an improvement of symptoms associated with Evaporative Dry Eye and Stage 2 MGD when a liposome spray, namely Tears Again® advanced Liposome Spray, was added to treatment plans. Compared with hyaluronate eye drops and triglyceride gels, the liposome spray was significantly more effective at reducing lid margin inflammation and improving tear film stability.
Utilizing patented liposome technology to deposit water and lipids as well as vitamins A, C, and E, Tears Again® advanced Liposome Spray provides moisture to soothe and relieve discomfort. Simply spray the cool, refreshing mist onto closed eyelids throughout the day as often as needed.
For a complete eyelid hygiene regimen, use Tears Again® advanced Liposome Spray in conjunction with OCuSOFT® Lid Scrub™ Eyelid Cleansers, which are also conveniently available at your local CVS.
For more information, visit www.tearsagainspray.com or call (800) 233-5469.
*Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, Lemp MA, Sullivan DA. The International Workshop on Meibomian Gland Dysfunction, Investigative Ophthalmology & Visual Science, Special Issue 2011, Vol. 52, No. 4

Drug development: RGN259 Phase II trial underway

2011-09-21T19:20:00.000-07:00

Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye (clinicaltrials.gov page)

Newsblurb from August 26

RegeneRx Biopharmaceuticals reported enrolling all 72 patients in its phase 2 trial of its RGN-259 treatment for dry-eye syndrome.

Patients will receive RGN-259 or a placebo twice daily until Sept. 23. The Rockville biotech expects preliminary data available in October.

In animal models, RGN-259 worked better than Restasis — the only FDA-approved drug for dry-eye syndrome — for certain conditions, according to a RegeneRx statement.

Abstract: Safety of re-using Refresh Plus vials

2011-09-21T19:09:00.000-07:00

This is an interesting study that raises lots of questions about re-use of preservative free eyedrop vials.

There are many eyedrops in "single-use vials" which are common used by people with dry eye, from OTC preservative-free lubricants to Restasis. Most are so costly and entail so much waste if used only once that they are often re-used. Many doctors support such re-use and some manufacturers may as well. In the early days of Restasis I seem to recall they even provided a little contraption to store them safely for re-use. We see debates now and then on the bulletin board as to whether refrigeration is appropriate.

This study basically says that for a vial of Refresh Plus (pretty much the most commonly used artificial tear on the market), if the common bacterium pseudomonas aeruginosa gets in it, it will thrive and could do some nasty things to your cornea. Not good.

At the very least this sounds like a cautionary word for users of unpreserved carboxymethylcellulose-based artificial tears, i.e. if you're re-using them, you may want to reconsider. I would be interested to know of it has implications for other polymer-based unpreserved drops. This is certainly enough to make me reconsider whether I suggest to anyone that they carefully re-use vials.

Pseudomonas aeruginosa Growth in Refresh Plus(®).

Abstract Purpose:
To assess Pseudomonas aeruginosa growth in Refresh Plus(®), a unit-dose preservative-free ophthalmic solution indicated for the treatment of dry eye and after laser-assisted in situ keratomileusis (LASIK) surgery, which contains carboxymethylcellulose 0.5% as its active ingredient.

Methods:
Multiple test tubes of Refresh Plus were inoculated with 3 clinical ocular isolates of P. aeruginosa to achieve a target concentration of ∼100 colony-forming units (CFU)/mL. The tubes were incubated at 25°C and samples were aseptically removed at 6, 12, and 24 h. The samples were cultured to enumerate the population at each time point.

Results:
After 6 h incubation, the number of CFU/mL was 3,200 for isolate 1, 2,000 for isolate 2, and 6,480 CFU/mL for isolate 3. For all 3 organisms tested, the number of CFU/mL after 12 and 24 h incubation was >10(6) CFU/mL.

Conclusions:
Under the conditions of this experiment, Refresh Plus appears to support P. aeruginosa growth, suggesting that if the solution in a unit-dose vial of Refresh Plus were contaminated with P. aeruginosa during use, the organism would survive and replicate in the solution over time. Noncompliance with the manufacturer's recommendations (i.e., reuse of an open vial) may result in contamination of the solution with P. aeruginosa, which may cause severe keratitis.

J Ocul Pharmacol Ther. 2011 Aug 12. [Epub ahead of print]
Pinna A, Usai D, Zanetti S.
Source
1 Section of Ophthalmology, Department of Surgery, Microsurgery, and Medico-surgical Specialties, University of Sassari , Sassari, Italy .

Abstract: Omega 3/Omega 6 dry eye study

2011-08-15T18:12:00.000-07:00

Hm. These results are really quite disappointing all things considered. No, it doesn't mean stop taking your fish oil - as long as you've got a good one, it's good for you even if it isn't helping your eyes :-)

A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients.

Purpose:
To determine whether oral supplementation with omega-3 and omega-6 fatty acids can reduce conjunctival epithelium expression of the inflammatory marker human leucocyte antigen-DR (HLA-DR) in patients with dry eye syndrome (DES).

Methods:
This 3-month, double-masked, parallel-group, controlled study was conducted in nine centres, in France and Italy. Eligible adult patients with mild to moderate DES were randomized to receive a placebo containing medium-chain triglycerides or treatment supplement containing omega-3 and omega-6 fatty acids, vitamins and zinc. Treatment regimen was three capsules daily. Impression cytology (IC) was performed at baseline and at month 3 to assess the percentage of cells expressing HLA-DR and to evaluate fluorescence intensity, an alternate measure of HLA-DR. Dry eye symptoms and objective signs were also evaluated. Analyses were performed on the full analysis set (FAS) and per-protocol set (PPS).

Results:
In total, 138 patients were randomized; 121 patients with available IC were included in the FAS, and of these, 106 patients had no major protocol deviations (PPS). In the PPS, there was a significant reduction in the percentage of HLA-DR-positive cells in the fatty acids group (p = 0.021). Expression of HLA-DR as measured by fluorescence intensity quantification was also significantly reduced in the fatty acids group [FAS (p = 0.041); PPS (p = 0.017)]. No significant difference was found for the signs and symptoms, but there was a tendency for improvement in patients receiving the fatty acids treatment.

Conclusion: This study demonstrates that supplementation with omega-3 and omega-6 fatty acids can reduce expression of HLA-DR conjunctival inflammatory marker and may help improve DES symptoms.

Acta Ophthalmol. 2011 Aug 11. doi: 10.1111/j.1755-3768.2011.02196.x. [Epub ahead of print]
Brignole-Baudouin F, Baudouin C, Aragona P, Rolando M, Labetoulle M, Pisella PJ, Barabino S, Siou-Mermet R, Creuzot-Garcher C.
Department of Toxicology, Faculty of Biological and Pharmacological Sciences, Paris Descartes University, Paris, France INSERM, U968, Paris, France UPMC Univeristy Paris 06, UMR S 968, Institute of Vision, Paris, France CNRS, UMR 7210, Paris, France Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, France Department of Ophthalmology, University of Messina, Messina, Italy Clinica Oculista, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy CHU Bicêtre Department of Ophthalmology, Assistance Publique, South Paris University, Kremlin-Bicêtre, Paris, France Department of Ophthalmology, University François Rabelais, Bretonneau Hospital, Tours, France Bausch & Lomb, Montpellier, France Department of Ophthalmology, University Hospital, Dijon, France.

Abstract: The latest on sea buckthorn oil

2011-08-15T18:06:00.000-07:00

It's always tempting to think... ain't got enough oil? No prob, let's add some systemically or topically. Only, it is never quite that simple.

Remember last year's study of sea buckthorn oil and dry eye? This new study takes it in another direction, indicating that whatever good SBO is doing, it's not acting directly on the lipids but possibly on inflammation or through another mechanism.

Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye.

PURPOSE:
: Evaporative dry eye is associated with meibomian gland dysfunction and abnormalities of the tear film lipids. Dry eye is known to be affected positively by intake of linoleic and γ-linolenic acids and n-3 fatty acids. Oral sea buckthorn (Hippophaë rhamnoides) (SB) oil, which contains linoleic and α-linolenic acids and antioxidants, has shown beneficial effects on dry eye. The objective was to investigate whether supplementation with SB oil affects the composition of the tear film fatty acids in individuals reporting dry eye.

METHODS:
: One hundred participants were randomized to this parallel, double-blind, placebo-controlled study, which 86 of them completed. The participants daily consumed 2 g of SB or placebo oil for 3 months. Tear film samples were collected at the beginning, during, and at the end of the intervention and 1 to 2 months later. Tear film fatty acids were analyzed as methyl esters by gas chromatography.

RESULTS:
: There were no group differences in the changes in fatty acid proportions during the intervention (branched-chain fatty acids: P = 0.49, saturated fatty acids: P = 0.59, monounsaturated fatty acids: P = 0.53, and polyunsaturated fatty acids: P = 0.16).

CONCLUSIONS:
: The results indicate that the positive effects of SB oil on dry eye are not mediated through direct effects on the tear film fatty acids. Carotenoids and tocopherols in the oil or eicosanoids produced from the fatty acids of the oil may have a positive effect on inflammation and differentiation of the meibomian gland cells.

Cornea. 2011 Sep;30(9):1013-9.
Järvinen RL, Larmo PS, Setälä NL, Yang B, Engblom JR, Viitanen MH, Kallio HP.
Source
From the Department of *Biochemistry and Food Chemistry and †Department of Ophthalmology, University of Turku, Turku, Finland; ‡Turku School of Economics, University of Turku, Turku, Finland; §Turku City Hospital, Turku, Finland; and ¶Karolinska Institutet, Stockholm, Sweden.

Abstract: Optimizing lissamine green staining evaluation

2011-08-15T17:58:00.000-07:00

Optimizing evaluation of Lissamine Green parameters for ocular surface staining.

Purpose
The recently published seminal dry eye workshop proceedings defined Lissamine Green (LG), an organic dye, as a gold standard for demonstrating ocular surface staining. The purpose of the current study was to determine the optimal parameters of 1% LG instillation for the ocular surface examination in dry eye patients.

Design
Prospective and observational quality improvement study.

Methods
A quality improvement study evaluated 16 eyes from eight dry eye patients with different levels of severity. LG (1%), in three volumes (5, 10, and 20 μl) was instilled into the conjunctival cul-de-sac, and four masked observers with different levels of clinical expertise examined the patients with and without red filter. The staining pattern of the conjunctiva and cornea was documented with the Oxford scale within 4 min of LG instillation. Optimal volume and inter-observer reliability were assessed.

Results
All dye volumes were tolerated well by all patients. Experienced observers preferred 10 μl volume because of the ease of examination and accuracy. Although instillation of 20 μl yielded similar scores as 10 μl, it resulted in overflow of the lid and facial skin staining. The use of red filter significantly improved reading scores (P<0.01). Inter-observer reliability was higher for conjunctival scores than for corneal scores for all patients. The highest reliability was demonstrated with 10 μl volume and increased with greater experience of the observer.

Conclusions
Ocular surface examination with instillation of 10 μl 1% LG has good inter-observer reliability and is well tolerated. Observation through a red filter facilitates the examination

Eye (Lond). 2011 Aug 12. doi: 10.1038/eye.2011.184. [Epub ahead of print]
Hamrah P, Alipour F, Jiang S, Sohn JH, Foulks GN.
Source
1] Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA [2] Cornea and Refractive Surgery Service, Massachusetts Ear and Eye Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Abstract: Alterations of tear neuromediators in dry eye disease.

2011-08-15T17:55:00.000-07:00

Alterations of tear neuromediators in dry eye disease.

OBJECTIVES:
To evaluate tear levels of neuromediators in patients with dry eye disease and to identify statistical correlations with the clinical findings.

METHODS:
Nineteen patients with dry eye disease (Sjögren syndrome, n = 5 patients; non-Sjögren syndrome, n = 10; and ocular cicatricial pemphigoid, n = 4) and 12 healthy volunteers were enrolled. The eyes of all participants were evaluated by slitlamp examination, Schirmer testing, fluorescein staining, and tear film break-up time. Grading of dry eye severity was recorded. Tear samples were collected, and substance P, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nerve growth factor (NGF) concentrations were evaluated by enzyme-linked immunoassay and correlated with the clinical findings.

RESULTS:
Nerve growth factor tear levels were significantly increased in participants with dry eye disease; CGRP and NPY concentrations were significantly decreased when compared with those in healthy participants. Dry eye severity showed a direct correlation with NGF and an inverse correlation with CGRP and NPY tear levels. Nerve growth factor tear levels showed a direct correlation with conjunctival hyperemia and fluorescein staining results, CGRP directly correlated with Schirmer test values, and NPY inversely correlated with tear film break-up time. Subgroup analysis showed that CGRP and NPY but not NGF were changed in autoimmune (ie, Sjögren syndrome and ocular cicatricial pemphigoid) dry eye disease.

CONCLUSIONS:
The decreased tear levels of NPY and CGRP in dry eye disease are related to impaired lacrimal function, and tear levels of NGF are more closely related to corneal epithelial damage. Our findings suggest that NPY, CGRP, and NGF could become useful markers of dry eye severity.

Arch Ophthalmol. 2011 Aug;129(8):981-6.
Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S.
Source
Department of Ophthalmology, University of Rome, Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Rome, Italy. s.bonini@unicampus.it.

Abstract: Lit review of ocular surface harm from eyedrops.

2011-08-15T15:46:00.000-07:00

Wish I had access to the full study. The finding/summary points are such important things to keep in mind. I find myself getting more and more routinely concerned about potential harm from overdoing pharmaceutical dry eye therapies. Obviously there is no clear-cut answer to determining what's causing what - but there is good solid reason to go slow, not do too much at once, and observe carefully for changes.

Ocular surface damage by ophthalmic compounds.

PURPOSE OF REVIEW:
To describe the changes of the ocular surface following chronic use of eye drop therapies. The possible pathogenetic mechanisms responsible for specific signs and symptoms are described and discussed.

RECENT FINDINGS:
Topical treatments for ocular diseases may trigger an inflammatory response in predisposed patients, with local activation of immune cells and ocular surface damage. The resulting clinical picture may vary substantially, from mild to severe, sharing a red eye as a hallmark presentation. Recent in-vitro, in-vivo, and clinical data suggest that these detrimental effects are not solely related to eye drop preservatives and may be caused by the medication itself, especially for patients with preexisting ocular diseases. However, no specific tests are currently available to make a clear cut diagnosis between what is caused by the disease and what is the effect of its therapy. Patients' history and clinical features remain essential to hypothesize the underlying pathogenetic mechanism.

SUMMARY:
Topical therapies may induce ocular surface allergic reactions, dry eye-like reactions, and epithelial damage. Patients in need of chronic therapies are at higher risk of facing these detrimental effects of eye drop therapies and should be treated with unpreserved compounds.

Curr Opin Allergy Clin Immunol. 2011 Aug 4. [Epub ahead of print]
Mantelli F, Tranchina L, Lambiase A, Bonini S.
Source
aDepartment of Ophthalmology, Campus Bio-Medico, University of Rome bDepartment of Biopathology, Ophthalmology Division, UOSD Glaucoma, University of Rome 'Tor Vergata', Rome, Italy.

Abstract: Scleral lenses in SJS

2011-08-15T15:43:00.000-07:00

I find this sort of thing (90% success of SJS patients adapting to scleral lenses?!) very hopeful. One of the reasons people are so reluctant to try sclerals is that it seems counterintuitive to put a big lens in a dry eye. However, the results over the years show many people with very severe dry eye wearing them successfully. I'd really like to know how the 7 patients in this study fare a couple of years on - whether they're all wearing lenses full time.

PURPOSE:
To evaluate the efficacy of scleral contact lenses use on the management of ocular sequelae from Stevens-Johnson syndrome patients.

METHODS:
In a retrospective study, patients who suffered sequelae of Stevens-Johnson syndrome and started the use of scleral contact lenses were followed. Patients were submitted to an evaluation of symptoms through a questionnaire; ophthalmologic exam (visual acuity measurement, biomicroscopy, ocular surface staining with fluorescein drops, Schirmer test).

RESULTS:
Ten eyes of seven patients were analyzed. Visual acuity varied from hand movements to 20/25. All patients presented some degree of corneal opacity and slight symblepharon. In patients whose adaptation to scleral contact lenses was successful (90%), they all refered improvement of symptoms and sight. As for the biomicroscopic findings it was observed an improvement of conjunctival hyperemia and keratitis and a reduction of the mucous secretion in 90% the cases.

CONCLUSIONS:
A successful adaptation to scleral contact lenses was feasible on most patients, with relief of symptoms and better visual acuity, probably due to regularization of the surface. Scleral contact lenses represent an important and accessible alternative to reduce the limitations inferred by the damages from Stevens-Johnson syndrome.

Arq Bras Oftalmol. 2010 Oct;73(5):428-32.
[Scleral contact lens for ocular rehabilitation in patients with Stevens-Johnson syndrome].
[Article in Portuguese]
Siqueira AC, Santos MS, Farias CC, Barreiro TR, Gomes JÁ.
Source
Departamento de Oftalmologia, Instituto da Visão, Universidade Federal de São Paulo, SP, Brasil. anacarolinapunzi@yahoo.com.br

Abstract: Neural basis of spontaneous blinks

2011-08-15T15:41:00.000-07:00

Only sort of tangentially related to dry eye but I found this interesting... bearing in mind the chicken-and-egg relationship between dry eye and blinking.

Characterizing the spontaneous blink generator: an animal model.

Although spontaneous blinking is one of the most frequent human movements, little is known about its neural basis. We developed a rat model of spontaneous blinking to identify and better characterize the spontaneous blink generator. We monitored spontaneous blinking for 55 min periods in normal conditions and after the induction of mild dry eye or dopaminergic drug challenges. The normal spontaneous blink rate was 5.3 ± 0.3 blinks/min. Dry eye or 1 mg/kg apomorphine significantly increased and 0.1 mg/kg haloperidol significantly decreased the blink rate. Additional analyses revealed a consistent temporal organization to spontaneous blinking with a median 750 s period that was independent of the spontaneous blink rate. Dry eye and dopaminergic challenges significantly modified the regularity of the normal pattern of episodes of frequent blinking interspersed with intervals having few blinks. Dry eye and apomorphine enhanced the regularity of this pattern, whereas haloperidol reduced its regularity. The simplest explanation for our data is that the spinal trigeminal complex is a critical element in the generation of spontaneous blinks, incorporating reflex blinks from dry eye and indirect basal ganglia inputs into the blink generator. Although human subjects exhibited a higher average blink rate (17.6 ± 2.4) than rats, the temporal pattern of spontaneous blinking was qualitatively similar for both species. These data demonstrate that rats are an appropriate model for investigating the neural basis of human spontaneous blinking and suggest that the spinal trigeminal complex is a major element in the spontaneous blink generator.

J Neurosci. 2011 Aug 3;31(31):11256-67.
Kaminer J, Powers AS, Horn KG, Hui C, Evinger C.
Source
Department of Psychology, Program in Neuroscience, and Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, New York 11794-5230, and SUNY Eye Institute.

Abstract: DA-HSV to diagnose dry eye

2011-08-15T15:35:00.001-07:00

Nothing exciting here. When a diagnostic device has something intelligent and reproducible to say about severity levels, then it almost starts to get interesting.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy.

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area high-speed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring's regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion, this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

J Biomed Opt. 2011 Jul;16(7):076012.
Alonso-Caneiro D, Turuwhenua J, Iskander DR, Collins MJ.
Source
Queensland University of Technology, School of Optometry, Victoria Park Road, Kelvin Grove, QLD 4059 Brisbane, AustraliaAuckland Bioengineering Institute and the Department of Optometry and Vision Science, University of Auckland, Auckland, New ZealandInstitute of Biomedical Engineering and Instrumentation, Plac Grunwaldzki 13, 50-377 Wroclaw, Poland.

Abstract: FD-OCT measurement of tear meniscus

2011-08-15T15:25:00.001-07:00

Tear meniscus ain't everything, not by a long shot, but still... those who complain their eyes feel the same 5 minutes after putting in drops could understandably be tempted to think this explains how they feel.

Serial Measurement of Tear Meniscus by FD-OCT After Instillation of Artificial Tears in Patients With Dry Eyes.

BACKGROUND AND OBJECTIVE:
To use Fourier-domain optical coherence tomography (FD-OCT) to study the effect of artificial tears on the tear meniscus in patients with dry eyes.

PATIENTS AND METHODS:
The lower tear meniscus of 16 consecutive patients with dry eyes was imaged by an FD-OCT system (RTVue; Optovue, Inc., Fremont, CA). Baseline and five serial pairs of measurements were taken after the instillation of artificial tears (Optive; Allergan, Irvine, CA) at 1, 2, 5, 10, and 15 minutes. The lower meniscus height, depth, and area were measured with a computer caliper.

RESULTS:
Baseline meniscus measurements were 235.5 ± 150.0 μm, 138.1 ± 78.7 μm, and 0.020 ± 0.022 mm(2) for height, depth, and area, respectively. After instillation of artificial tears, all lower tear meniscus parameters remained significantly elevated for 5 minutes and returned to baseline by 10 minutes.

CONCLUSION:
FD-OCT is able to quantify a dramatic initial increase in tear meniscus, followed by a decay back to baseline values after approximately 5 minutes. FD-OCT may be useful in objectively quantifying the dynamic efficacy of dry eye treatments.

Ophthalmic Surg Lasers Imaging. 2011 Jul-Aug;42(4):308-13. doi: 10.3928/15428877-20110603-02.
Bujak MC, Yiu S, Zhang X, Li Y, Huang D.

Drug updates: Disappointing Remura results

2011-08-15T15:16:00.000-07:00

SeekingAlpha says:

Executives blamed a “dramatic” placebo response

Jeepers creepers, if that ain't a lesson in attempting to spin the unspinnable. Sigh. Let's hope the EAST study (see below) fares better.

ISTA Pharmaceuticals Reports Results From the First of Two Trials in the REMURA(TM) Phase 3 Clinical Program for Dry Eye Disease

IRVINE, CA, Jul 28, 2011 (MARKETWIRE via COMTEX) -- ISTA Pharmaceuticals, Inc. ISTA +11.29% , today announced top-line results from the first of its two Phase 3 studies to evaluate the short-term safety and efficacy of two concentrations of REMURA(TM) (bromfenac ophthalmic solution for dry eye) in alleviating the signs and symptoms of dry eye disease. The company's Phase 3 safety and efficacy program, which consists of two studies known as EAST and WEST, is being conducted under a Special Protocol Assessment (SPA) agreed upon with the U.S. Food and Drug Administration (FDA). Today's top-line results are from the WEST study; the EAST study is now fully enrolled and the Company expects to announce top-line results from the EAST study during fourth quarter of 2011.

According to preliminary analysis of the top-line results from the WEST study, while REMURA was highly effective in treating a sign and symptom of dry eye, it was not statistically significantly better than placebo, a common outcome reported in studies testing other dry eye therapies. From baseline, both concentrations of REMURA and the placebo showed highly statistically significant improvement (p < 0.0001) in one sign and one symptom. The co-primary end-points identified in the SPA require REMURA to achieve a statistically significant difference from placebo, not baseline, which was not achieved in the WEST Study.

In analyzing the patient data, the higher concentration of REMURA achieved statistical significance against placebo in the sign of conjunctival staining as measured using the Lissamine Green (LG) Staining test among a sub-population of female patients 51-70 years of age with moderate dry eye disease. Safety data demonstrated REMURA was well-tolerated, with an adverse event profile similar to placebo and consistent with those observed previously with REMURA in a Phase 2 study and with other prescription dry eye drops. All three formulations were rated by patients as very comfortable.

"Consistent with our Phase 2 Study data, today's results show REMURA has a significant impact on the signs and symptoms of dry eye when compared to baseline. Since REMURA did not meet its co-primary end points in the WEST study, armed with this data, we expect to amend the statistical plan to appropriately focus the EAST study," stated Timothy R. McNamara, Pharm.D., Vice President of Clinical Research and Medical Affairs of ISTA Pharmaceuticals. "The EAST study is now fully enrolled, but the database has not been locked. We continue to analyze the WEST data, and once we see the data from the EAST Study, which we plan to announce in the fourth quarter, we'll make decisions about future development plans."

Drug updates: RGN-259 starting (another?) Phase 2 trial

2011-08-15T13:40:00.002-07:00

RegeneRx to start RGN-259 Phase 2 trial
July 29

US based drug developer RegeneRx Biopharmaceuticals has decided to start a placebo-controlled, double-masked Phase 2 trial for evaluating the efficacy and safety of RGN-259 in patients with dry eye syndrome soon.

The trial which will be conducted by ORA, an ophthalmic contract research organization, will start patient enrollment in next month.

In the trial, the patients will be given RGN-259 or placebo twice daily for 30 days.

Previously, RGN-259 has demonstrated reduction in corneal damage associated with dry eye syndrome in two animal models when compared to both positive and negative controls.

RegeneRx president and CEO Finkelstein said they have received Institutional Review Board approval for the trial, completed manufacturing of RGN-259 and placebo, and are currently preparing for enrollment of the first patients.

"This is a very important clinical trial for RegeneRx that is based on a body of human and preclinical data that suggest RGN-259 could have beneficial effects in treating dry eye," Finkelstein said.

Abstract: About tear lipocalins

2011-08-15T13:40:00.001-07:00

Tear lipocalin: structure and function.

Lipocalins are a family of diverse low molecular weight proteins that act extracellularly. They use multiple recognition properties that include 1) ligand binding to small hydrophobic molecules, 2) macromolecular complexation with other soluble macromolecules, and 3) binding to specific cell surface receptors to deliver cargo. Tear lipocalin (TLC) is a major protein in tears and has a large ligand-binding cavity that allows the lipocalin to bind an extensive and diverse set of lipophilic molecules. TLC can also bind to macromolecules, including the tear proteins lactoferin and lysozyme. The receptor to which TLC binds is termed tear lipocalin-interacting membrane receptor (LIMR). LIMR appears to work by endocytosis. TLC has a variety of suggested functions in tears, including regulation of tear viscosity, binding and release of lipids, endonuclease inactivation of viral DNA, binding of microbial siderophores (iron chelators used to deliver essential iron to bacteria), serving as a biomarker for dry eye, and possessing anti-inflammatory activity. Additional research is warranted to determine the actual functions of TLC in tears and the presence of its receptor on the ocular surface.

Ocul Surf. 2011 Jul;9(3):126-38.
Dartt DA.
Source
From the Schepens Eye Research Institute and Harvard Medical School, Boston, MA.

Abstract: Mustard gas & dry eye

2011-08-15T13:34:00.000-07:00

I know I'm a broken record but... anybody with severe enough dry eye to be considering tarsorrhaphy, AMT etc (per below) should be considered for PROSE/scleral referral or at least informed of this option before invasive surgeries.

Sulfur mustard-induced ocular surface disorders.

Sulfur mustard is a vesicant agent with severe irritating effects on living tissues, including skin, mucous membranes, eyes, and respiratory tract. The eyes are the most susceptible tissue to mustard gas effects, and varying degrees of ocular involvement are seen in 75% to 90% of exposed individuals. Most cases resolve uneventfully; however, a minority of exposed patients will have a continuous process, which manifests clinically either as a persistent smoldering inflammation (chronic form) or late-onset lesions appearing many years after a variable "silent" period (delayed form). Distinctive features common to most cases with chronic involvement include chronic blepharitis, meibomian gland dysfunction, dry eye, limbal ischemia, limbal stem cell deficiency, aberrant conjunctival vessels, corneal neovascularization, and secondary degenerative changes, including lipid and amyloid deposition and corneal irregularity, thinning and scarring. Most cases can be managed with conservative measures, eg, preservative-free artificial tears, lubricants, and topical steroids. Punctal plugs or punctal cauterization is helpful in moderate and severe forms of injury. Surgical modalities, including lateral or medial tarsorrhaphies, amniotic membrane transplantation, lamellar or penetrating keratoplasty, and stem cell transplantation have been used.

Ocul Surf. 2011 Jul;9(3):163-78.
Baradaran-Rafii A, Eslani M, Tseng SC.
Source
From the Ophthalmic Research Center, Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences.

Abstract: SAR1118 in dogs

2011-08-15T13:33:00.000-07:00

For those of you following SAR-1118 developments....

The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs.

PURPOSE:
Keratoconjunctivitis sicca (KCS) is characterized by inflammation and decreased production of tears containing increased levels of cytokines. The release occurs in the setting of conjunctival and lacrimal gland inflammation, potentially mediated by the interaction between lymphocyte function-associated antigen (LFA)-1, a cell surface protein found on lymphocytes, and its cognate ligand intercellular adhesion molecule (ICAM)-1. SAR 1118 is a novel LFA-1 antagonist and may be an effective therapeutic agent for the treatment of KCS. The following studies were performed to assess the in vitro activity of SAR 1118 and to evaluate the clinical efficacy of topical SAR 1118 for the treatment of idiopathic canine KCS.

METHOD:
Pharmacodynamics were assessed by measuring the ability of SAR 1118 to inhibit Jurkat T-cell binding with recombinant human ICAM-1 and to inhibit cytokine release from human peripheral blood mononuclear cells (PBMCs) stimulated by staphylococcal enterotoxin B. For the assessment of clinical efficacy, 10 dogs diagnosed with idiopathic KCS were treated with SAR 1118 1% topical ophthalmic solution three times daily for 12 weeks. Schirmer's tear test (STT) was used to measure tear production.

RESULTS:
SAR 1118 demonstrated concentration-dependent inhibition of Jurkat T-cell attachment, inhibition of lymphocyte activation, and release of inflammatory cytokines, particularly the Th1, Th2, and Th17 T-cell cytokines IFN-γ, IL-2, and IL-17F, respectively. Mean STT values increased from 3.4 mm during week 1 to 5.8 mm at week 12 (P < 0.025). No SAR 1118-related adverse events were observed.

CONCLUSIONS:
SAR 1118 appears to be an effective anti-inflammatory treatment for KCS. Additional studies are warranted to establish the efficacy of SAR 1118 for the treatment of KCS in humans.

Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. Print 2011 May.
Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA.
Source
School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA. murphyc@corl.vetmed.wisc.edu

Article: Scleral lens fitting

2011-08-15T13:28:00.000-07:00

...And in that same CLS issue there's a great article by Lynette Johns OD of Boston Foundation for Sight discussing scleral lens fitting on dry-eyed folks from the doctor's perspective:

Fitting Scleral Lenses for Ocular Surface Disease
Defining fitting goals and patient expectations is an important first step in managing OSD with sclerals.

The resurgence of scleral lenses in GP materials has opened up many opportunities for fitting complex corneas. In the setting of irregular astigmatism and keratectasias (keratoconus, keratoglobus, pellucid marginal degeneration, and post-laser-assisted in situ keratomileusis [LASIK] ectasia), many patients who were unable to be optimally fit with corneal GP lenses have another non-surgical alternative to consider. The use of scleral lenses to visually rehabilitate these patients is equally rewarding for both the patients and the providers, especially when surgery can be avoided....

Article: Corneal stem cells

2011-08-15T13:22:00.001-07:00

Sorry I didn't post this sooner... made a note of it and never got to it. Back in July there was a really nice CLS article by Drs. Mastrota and Townsend on corneal stem cells... If you have run across my links to items on limbal stem cell deficiency (LSCD) now and then and want to better understand what that is, click on this and read the full article:

A Closer Look at Corneal Stem Cells
Early intervention by practitioners can prevent and aid treatment of limbal stem cell deficiency.

We would imagine that similar to most of us, you confidently assure uncomfortable patients who have a corneal abrasion that the injury will heal relatively quickly with a good chance that their vision will be uncompromised. We daily take for granted the remarkable architecture and exquisite processes that create and regenerate the optically clear cornea.

How does the cornea maintain itself? How do superficial corneal abrasions heal? Why does corneal staining go away? Why can a cornea become vascularized?....

Abstract: Osmolarity and Sjogrens, again

2011-08-02T10:07:00.000-07:00

Tear Osmolarity Measurements in Dry Eye Related to Primary Sjögren's Syndrome.

Background:
To evaluate the tear osmolarity in patients with dry eye syndrome related to primary Sjögren's Syndrome (SS).

Materials and Methods:
Twenty eyes of 10 patients with dry eye and primary SS (Group 1) and 20 eyes of 20 subjects who do not have dry eye syndrome (Group 2) were included in this cross-sectional study. In all eyes, ophthalmic examination was performed in the same order: International Ocular Surface Disease Index survey, visual acuity assessment, conjunctival hyperemia scoring, tear osmolarity measurement with TearLab(™) Osmolarity System, tear film break-up time assessment, corneal fluorescein staining scoring, ocular surface Lissamine Green staining scoring, anesthetized Schirmer test. Dry eye severity was graded according to Dry Eye Workshop (DEWS) classification system.

Results: Four eyes with grade 1, four eyes with grade 2, seven eyes with grade 3, and five eyes with grade 4 dryness, according to DEWS system, were included. The mean tear osmolarity value was 301.9 ± 11.40 mOsm/L (range: 290-328) in Group 1, and 294.85 ± 8.33 mOsm/L (range: 283-311) in Group 2 (p = 0.03). In Group 1, tear osmolarity values were positively correlated with OSDI scores (r(18) = 0.55, r(2) = 0.31, p = 0.01), DEWS classification grades (r(18) = 0.73, r(2) = 0.54, p < 0.01), temporal and total corneal staining scores (r(18) = 0.67, r(2) = 0.44, p < 0.01, and r(18) = 0.51, r(2) = 0.26, p = 0.02, respectively), temporal conjunctival staining scores (r(18) = 58, r(2) = 0.34, p < 0.01); and negatively correlated with anesthetized Schirmer test results (r(18) = -0.62, r(2) = 0.38, p < 0.01) and TFBUT (r(18) = -0.50, r(2) = 0.25, p = 0.02).

Conclusions: Tear osmolarity values were found to be greater in patients with dry eye syndrome related to primary SS compared to control subjects, and positively correlated with the severity of dry eye.

Curr Eye Res. 2011 Aug;36(8):683-90.
Utine CA, Bıçakçıgil M, Yavuz S, Ciftçi F.
Yeditepe University, Department of Ophthalmology , Istanbul , Turkey.

Abstract: Role of EMMPRIN in dry eye

2011-07-25T13:44:00.000-07:00

Extracellular Matrix Metalloproteinase Inducer Modulates Epithelial Barrier Function through a Matrix Metalloproteinase-9-Mediated Occludin Cleavage: Implications in Dry Eye Disease.

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.

Am J Pathol. 2011 Jul 18. [Epub ahead of print]
Huet E, Vallée B, Delbé J, Mourah S, Prulière-Escabasse V, Tremouilleres M, Kadomatsu K, Doan S, Baudouin C, Menashi S, Gabison EE.
Source
CRRET Laboratory, Université Paris-Est, CNRS, Créteil, France; Department of Bioengineering, Institute of Technology, Université Paris-Est, Créteil, France.

Abstract: Dry eye and hepatitis C

2011-07-25T13:05:00.000-07:00

[Ocular surface and hepatitis C].
[Article in Portuguese]

PURPOSE:
To evaluate the outcomes of the tests used for dry eye diagnosis in patients with hepatitis C virus, and to verify if there is any relationship between the duration of illness and intensity of ocular surface changes.

METHODS:
25 patients with hepatitis C virus without treatment, and 29 patients with negative serologic tests for hepatitis C virus were selected. Biomicroscopy, tear film crystallization test, tear film break-up time, evaluation of the corneal staining with 1% fluorescein sodium, Schirmer I test, ocular surface staining with 1% rose bengal and esthesiometry were performed in both groups.

RESULTS:
In the Schirmer I test, the group of patients with hepatitis C displayed lower values in both eyes (OR p=0.0162; OS p=0.0265). For the tear film break-up time, there was a lower score in the group with hepatitis C, but it was statistically significant only in the left eye (p=0.0007). Regarding the ocular surface damage, the rose bengal staining test showed a higher average in the hepatitis group in both eyes (right p=0.0008; left p=0.0034). There was a difference in the average esthesiometry between the groups, being the average lower in infected patients (OR p=0.0006; OS p=0.0015). There was no linear association between time of hepatitis C infection and intensity observed in dry eye tests.

CONCLUSIONS:
Hepatitis C virus infection causes dry eye. Further researches are necessary to establish the physiopathology and the relationship with Sjögren syndrome.

Arq Bras Oftalmol. 2011 Apr;74(2):97-101.
Gomes RL, Marques JC, Albers MB, Endo RM, Dantas PE, Felberg S.
Source
Setor de Catarata, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.

Abstract: Inflammation and dry eye (aqueous vs MGD)

2011-07-25T07:25:00.000-07:00

This is a really interesting study looking at cytokines of patients with healthy tears, aqueous deficient dry eye and MGD dry eye. From this perspective, the MGD eye looks more like a healthy eye than an aqueous deficient eye.

Pro-inflammatory cytokine profiling of tears from dry-eye patients by means of antibody-microarrays.

Purpose:
In the pathogenesis of keratoconjunctivitis sicca immune processes are thought to play an important role. However, the exact details of the pathomechanisms are still unknown. In this study we analyzed the expression patterns of pro-inflammatory cytokines in the tears of patients suffering from different subtypes of dry-eye.

Methods:
143 subjects subdivided into healthy controls (CTRL, n=38), patients having an aqueous deficient dry-eye (DRYaq, n=35), patients showing changes of the lipid-layer (DRYlip, n=36) or a combination of both (DRYaplip, n=34) were examined. Expression patterns of proteins, e.g. IL-1β, IL-6, ITNFα and IFNγ, were examined using an advanced antibody microarray approach.

Results:
We detected several highly significant differences in the cytokine levels of dry-eye patients compared to healthy controls. In comparison to healthy subjects, patients suffering from aqueous deficient dry-eye or those with a combined pathogenesis showed elevated levels for most of the tested proteins. E.g. IL-1-β was found to be elevated 2.4 fold in DRYaq patients, respectively 2.75 fold in DRYaqlip patients (both P<8.00E-6). The detected protein amounts of patients suffering from dry-eye induced by lipid layer changes and healthy controls showed only minimal differences (fold increase/decrease for all proteins >1.2, P>0.5).

Conclusions:
The similarity between profiles of healthy controls and patients with a lipid layer induced dry-eye justifies the assumption that the pathomechanism of this dry-eye subtype is rather based on other mechanisms than inflammation, whereas it seems to be the case for patients suffering from aqueous deficient dry-eye.

Invest Ophthalmol Vis Sci. 2011 Jul 20. [Epub ahead of print]
Boehm N, Riechardt AI, Wiegand M, Pfeiffer N, Grus FH.
. Experimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Abstract: Severe Dry Eye Syndrome After Radiotherapy for Head-and-Neck Tumors.

2011-07-21T14:51:00.000-07:00

Severe Dry Eye Syndrome After Radiotherapy for Head-and-Neck Tumors.

PURPOSE:
To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy.

METHODS AND MATERIALS:
The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise.

RESULTS:
Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p < .0001 and p < .0001, respectively) and dose per fraction (p ≤ .0001 and p = .0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses < 45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES.

CONCLUSION:
With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation.

Int J Radiat Oncol Biol Phys. 2011 Jul 15. [Epub ahead of print]
Bhandare N, Moiseenko V, Song WY, Morris CG, Bhatti MT, Mendenhall WM.
Source
Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL.