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.