Wednesday, January 18, 2012

Abstract: Meibum expressibility scale

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

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?

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?

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

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?

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

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

...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

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

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

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

(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

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.

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

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.

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

Contact lens-related dry eye and ocular surface changes with mapping technique in long-term soft silicone hydrogel contact lens wearers.

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

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

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

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

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

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

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

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!

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