Friday, July 8, 2011

Abstract: MIM-D3

And while this drug is trucking along in clinical trials, an earlier study of it in a rat model was published:

An NGF mimetic, MIM-D3, stimulates conjunctival cell glycoconjugate secretion and demonstrates therapeutic efficacy in a rat model of dry eye.

The aim of this study was to evaluate the efficacy of MIM-D3, a small molecule nerve growth factor (NGF) peptidomimetic, as a therapeutic agent in rats with scopolamine induced dry eye. NGF plays an important role in ocular surface maintenance and corneal wound healing and was recently shown to have mucin secretagogue activity in conjunctival cells. We investigated whether MIM-D3 increased glycoconjugate secretion in conjunctival cells in vitro and in rat tear fluids in vivo. Primary rat conjunctival cell cultures were treated with increasing concentrations of MIM-D3 and evaluated for glycoconjugate secretion, proliferation and MAPK1/2 activation. Glycoconjugates were quantitated in tear fluids from normal rats treated topically with increasing doses of MIM-D3 (0.4%, 1% and 2.5%). Dry eye was induced in rats by subcutaneous scopolamine treatment, administered by surgically implanted osmotic pumps for 14 or 28 days. Aqueous tear production, tear clearance, fluorescein corneal staining and tear break-up time (tBUT) were evaluated. Glycoconjugates and NGF were quantitated in the tear fluids by enzyme-linked lectin assay (ELLA) and enzyme-linked immunosorbant assay (ELISA), respectively .We found that 50 μM MIM-D3 statistically significantly induced a 1.3-fold increase in glycoconjugate secretion and a 2.3-fold increase in MAPK1/2 activation without increasing proliferation from conjunctival cell cultures. Application of 2.5% MIM-D3 in normal rat eyes statistically significantly increased tear glycoconjugate concentration by 2.3-fold. In the experimental dry eye model, application of 1% MIM-D3 to rat eyes for either 1 or 17 consecutive days, followed by 1 week of no dosing produced a statistically significant decrease in corneal staining (p < 0.001), a slight increase in tBUT, and increases in tear glycoconjugates (p < 0.05) compared to vehicle. Scopolamine treatment also caused a statistically significant increase of endogenous NGF in tears (p < 0.005). We concluded that the increase in glycoconjugate concentration by the 1% MIM-D3 dose may have improved the quality and stability of the tear film, and thereby improved healing on the ocular surface in dry eye. Therefore, MIM-D3 may have therapeutic potential as a topical agent for the treatment of dry eye.

Exp Eye Res. 2011 Jun 25. [Epub ahead of print]
Jain P, Li R, Lama T, Saragovi HU, Cumberlidge G, Meerovitch K.
Mimetogen Pharmaceuticals, Montreal, Quebec, Canada.

Abstract: Tear stability after conjunctivochalasis surgery

I'd like to talk to some of these 15 patients to hear exactly how improved their symptoms were, say, a year after surgery. While I know conjunctivochalasis has to be addressed in some patients, I've rarely heard from anyone who had lasting benefit if their primary complaint was ocular surface discomfort. If you're one, let me know!

Evaluation of Tear Stability After Surgery for Conjunctivochalasis.

To evaluate the efficacy of surgical treatment for conjunctivochalasis using the Tear Film Stability Analysis System.

Fifteen eyes of 15 patients (74.5± 4.8 years; 14 females and 1 male) who had surgical reconstruction of the tear meniscus for conjunctivochalasis underwent evaluation with a symptom questionnaire, Schirmer I test, fluorescein tear film break-up time (FBUT), and break-up time index (BUI) measurement by Tear Film Stability Analysis System examinations that were performed preoperatively and 3 months after the surgery. Changes of these tear parameters were statistically analyzed using the paired t test.

After the surgery, the mean FBUT and BUI values significantly improved from 5.7± 3.2 s and 42.8± 18.7, respectively, to 8.4± 2.5 s and 60.7± 16.5, respectively (FBUT, p = 0.0438; BUI, p = 0.0036). The mean Schirmer test value showed no significant changes before and after surgery (p = 0.9064). Fourteen eyes (93.3%) had improvement of ocular symptoms after surgery. One eye (6.7%) with no improvement of ocular symptoms, FBUT, and BUI after surgery appeared to have aqueous tear deficiency.

CONCLUSIONS.: Surgical treatment for conjunctivochalasis was associated with improvement of tear stability and clinical dry eye symptoms.

Optom Vis Sci. 2011 Jun 23. [Epub ahead of print]
Hara S, Kojima T, Ishida R, Goto E, Matsumoto Y, Kaido M, Shimazaki J, Dogru M, Tsubota K.
*MD †MD, PhD Department of Ophthalmology, Social Insurance Chukyo Hospital, Aichi, Japan (SH), Johnson & Johnson Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo, Japan (TK, YM, MK, MD), Ishida Eye Clinic, Shizuoka, Japan (RI), Department of Ophthalmology, Tsurumi Dental College, Kanagawa, Japan (EG), Department of Ophthalmology, Tokyo Dental College, Chiba, Japan (JS), and Department of Ophthalmology, Keio University, Tokyo, Japan (TK, MK, KT).

Abstract: Double vital tear staining

Usefulness of Double Vital Staining With 1% Fluorescein and 1% Lissamine Green in Patients With Dry Eye Syndrome.

To determine the relative staining characteristics of the nasal and temporal conjunctiva as compared with other measures of dry eye and evaluate the qualitative clinical impression of the utility of the double vital staining with fluorescein and lissamine green.

Ocular surface staining was performed with a mixture of 1% fluorescein and 1% lissamine green in 50 patients with dry eye (12 patients with Sjögren syndrome and 38 patients with non-Sjögren syndrome). Ocular surface disease index (OSDI), tear breakup time (BUT), and Schirmer test were evaluated. Digital photographs were taken after vital staining on the ocular surface, and the grade of staining in various areas was assessed. Correlation among the degrees of staining, OSDI, and ocular surface parameters was analyzed.

The nasal conjunctiva evidenced greater staining compared with the temporal conjunctiva and cornea (P = 0.04). Staining of the nasal conjunctiva showed significant correlation with OSDI (P < 0.01) and BUT (P = 0.03). Staining of the temporal conjunctiva correlated significantly with OSDI (P = 0.01), and staining of the cornea correlated with BUT (P = 0.02).

Double vital staining with 1% fluorescein and 1% lissamine green correlates with symptoms and some ocular surface parameters in patients with dry eye and helps to identify ocular surface changes easily. It may be a useful method for the diagnosis of dry eye and the assessment of the therapeutic effect in patients with dry eye syndrome.

Cornea. 2011 Jun 22. [Epub ahead of print]
Yoon KC, Im SK, Kim HG, You IC.
From the *Department of Ophthalmology and Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju, Korea; and †Department of Ophthalmology, Chonbuk National University Medical School and Hospital, Jeonju, Korea.

Drug news: Mimetogen MIM-D3 reports positive Phase II results

Mimetogen Pharmaceuticals Inc. Announces Positive Top Line Data from Phase II Clinical Trial of MIM-D3 for Dry Eye Disease

(June 27)

Mimetogen Pharmaceuticals Inc. (“Mimetogen”) today announced positive top line data from a Phase II clinical trial with MIM-D3, its lead drug for the treatment of dry eye. The trial demonstrated statistically significant improvements in signs and symptoms with its low (1%) and high (5%) doses of MIM-D3, together with excellent safety and tolerability profiles. Mimetogen is in the process of completing its analysis of the data, and intends to present further details at a future medical conference.

“These preliminary results are very promising for the use of MIM-D3 for the treatment of dry eye disease” said Garth Cumberlidge, President and CEO of Mimetogen, adding: MIM-D3, a novel growth factor mimetic, represents a potential first-in-class therapy for the estimated $1 billion US market”.

The 150-patient phase II study utilized a controlled adverse environment (CAETM) chamber to measure dry eye patients' ability to withstand a stressful drying environment on the eye, and patient diaries to measure the severity of their dry eye symptoms over the course of the study. Patients were randomized to receive MIM-D3 low dose, MIM-D3 high dose or placebo twice/day over the course of a 28-day study.

Phase II Clinical Trial of MIM-D3 for Dry Eye Disease

Mimetogen’s lead drug candidate for the treatment of dry eye disease, MIM-D3, is a small molecule mimetic of nerve growth factor (NGF). NGF is a naturally occurring protein in the eyes that is responsible for the maintenance of corneal nerves and epithelium, mucin and tear production. In contrast to most other products in development or on the market, MIM-D3 is designed to quickly and directly improve the quality of the tears produced by the eyes whilst reducing clinical signs and symptoms such as chronic dryness and grittiness. Dry eye disease is estimated to be a $1 billion US market for which there is currently only one FDA-approved treatment.

The Phase II randomized, double-masked, multi-center, placebo-controlled trial was designed to evaluate the safety, tolerability and efficacy of MIM-D3 in improving both the signs and symptoms of dry eye.

Abstract: Omega 3/6 supplement modestly improved dry eye

[Efficacy assessment of Nutrilarm(®), a per os omega-3 and omega-6 polyunsaturated essential fatty acid dietary formulation versus placebo in patients with bilateral treated moderate dry eye syndrome.]
[Article in French]

Inflammation is one of the main mechanisms common to all forms of dry eye. Since polyunsaturated acids are known to show biological anti-inflammatory properties, the aim of this study was to evaluate the efficacy of dietary n-6 and n-3 fatty acids in patients suffering from ocular dryness.

One hundred and eighty-one patients diagnosed with bilateral moderate dry eye who were already treated with lachrymal substitutes were randomized in a double-blind international study to receive placebo or Nutrilarm(®) capsules (combination of omega-3 and omega-6), twice a day for 6 months. In all subjects, dryness feeling, overall subjective comfort, and ocular symptoms (burning, stinging, sandy and/or gritty sensation, light sensitivity, reflex tearing, and ocular fatigue) were evaluated at each visit. Furthermore, fluorescein tests (break-uptime and Oxford scheme) and lissamine green test were performed at each visit. The Schirmer test was performed at inclusion and after 6 months of treatment.

After 6 months of supplementation with Nutrilarm(®), both the BUT scores and ocular fatigue were significantly improved when compared with placebo (P=0.036 and P=0.044, respectively). There was a trend in favor of Nutrilarm(®) in terms of the efficacy evaluated by the investigator (P=0.061). Fewer patients experienced a feeling of severe dryness with Nutrilarm(®) compared with placebo after 6 months of treatment (2.5 and 9.3%, respectively), but the difference was not statistically significant.

Oral administration of a double supplementation dietary n-6 and n-3 fatty acids present an additional therapeutic advantage in patients suffering from ocular dryness who were already treated with lachrymal substitutes.

J Fr Ophtalmol. 2011 Jun 20. [Epub ahead of print]
Creuzot-Garcher C, Baudouin C, Labetoulle M, Pisella PJ, Mouriaux F, Meddeb-Ouertani A, El Matri L, Khairallah M, Brignole-Baudouin F.
CHU de Dijon, 3, rue du Faubourg-Raines, 21033 Dijon cedex, France.

Abstract: Glaucoma meds & dry eye, redux

...This study echoes what I was saying a few posts back, that it takes more than a year for glaucoma meds to start affecting the ocular surface.

Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication.

To uncover tear proteins associated with the chronic use of glaucoma medication using proteomic analysis, and to compare these proteins to those previously identified from primary dry eye disease.

Eighteen patients treated with topical anti-glaucoma medications and 10 normal age-matched subjects with no prior topical treatment were recruited for the study. Tears were collected usingSchirmer's strip and analyzed using iTRAQ for the tear proteins using mass spectrometry. Conjunctival samples were collected and RNA expression determined by PCR.

Of the 124 identified tear proteins (99% confidence, ProtScore ≥ 2.0), we found that the tear levels of S100A8, A9, mammaglobinB and 14-3-3 ζ/δ were significantly increased in the medicated group compared to non-medicated group, (P<0.05). For S100 A9, mammaglobin B and 14-3-3 ζ/δ, use of topical medication for less than 1 year did not reach statistical significance compared to non-medicated group. Eyes on topical medication for less than one year showed a decrease of proline-rich 4 protein tear level (p = 0.0049) compared to non-medicated group. The tear proteins detected in the medicated group differed from the primary dry eye group.

Duration of topical anti-glaucoma medications longer than one year may start to induce ocular surface inflammation. The inflammatory tear protein profile present in chronically medicated glaucoma eyes appears to be different to that found in primary dry eye. Identification of tear proteins specific to medicated glaucoma eyes will help to specifically develop targeted screening modalities and therapeutic agents different to current conventional dry eye management.

Invest Ophthalmol Vis Sci. 2011 Jun 22. [Epub ahead of print]
Wong TT, Zhou L, Li J, Tong L, Zhao SZ, Li XR, Yu SJ, Koh SK, Beuerman RW.
Singapore Eye Research Institute, Singapore.

Abstract: IS thicker goop better?

Sometimes a commonly held assumption is just that - having solid basis in common sense but quite possibly not being borne out by evidence when looked at scientifically. I am reminded by this study of what I learned from Dr. Holly's work so many years ago - that viscosity is not necessarily the answer to better or longer lasting lubrication. It was certainly borne out in my own experience, considering how all the thickest goop never worked as well for me as the drops he formulated.

This study looks at a survey of a large number of Sjogrens patients in the UK. Of all the people using lubricant drops, gels and ointments, the Sjogrens would probably be the ones most likely to be advised by their doctors (or simply figure out on their own) to try the thickest gels and ointments in search of longer lasting relief. However, the data do not conclusively show that they are finding this works for them.

Treatment of dry eye: An analysis of the British Sjögren's Syndrome Association comparing substitute tear viscosity and subjective efficacy.

This study aims to address the lack of independent subjective efficacy data on artificial tear substitutes in the treatment of dry eye due to the anecdotal association of 'thicker' products being more effective.

This is an independent study of the subjective use and efficacy of topical treatments used by members of the British Sjögren's Syndrome Association (BSSA) related to product viscosity. 2000 members of the BSSA were sent a questionnaire regarding their physical condition and the use of artificial tear substitutes. Viscosity analysis was performed on the most popular preparations. Statistical comparison is made between subjective efficacies related to substitute tear viscosity.

1088 patients responded giving information regarding their condition together with the subjective use and efficacy data of artificial tear substitutes. Visco-analysis was performed on the most popular preparations; these had more than 50 patients using them. In terms of subjective benefits related to viscosity for 'frequency' and 'duration' the data suggests a general trend toward viscous preparations being instilled less frequently and lasting longer; however this was not shown to be significantly correlated and some interesting comparisons are reported.

The results confirm high levels of ocular lubricant use in the BSSA population. Our data investigates the often-anecdotal evidence that thicker preparations are more effective. However, we did not find this correlation to be statistically significant suggesting further study into factors related to subjective product efficacy. These results lay foundations for the development of future products in the treatment of severe dry eye.

Cont Lens Anterior Eye. 2011 Jun 18. [Epub ahead of print]
Bhojwani R, Cellesi F, Maino A, Jalil A, Haider D, Noble B.
North Lincolnshire and Goole NHS Trust, Woodland Avenue, Goole DN14 6RX, United Kingdom; Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.

Abstract: A flap is a flap

This study says whether your flap was made by a keratome or a femtosecond laser is immaterial as regards potential for dry eye symptoms. Apparently not funded by a microkeratome manufacturer, either.

Dry eye after laser in situ keratomileusis with femtosecond laser and mechanical keratome.
To prospectively compare dry-eye symptoms after laser in situ keratomileusis (LASIK) with mechanical keratome-created flaps and femtosecond laser keratome-created flaps.

Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA.

Randomized clinical trial.

Fellow eyes were prospectively randomized to the mechanical keratome group and femtosecond laser keratome group. Patients had wavefront-guided LASIK using a mechanical keratome in 1 eye and a femtosecond laser keratome in the fellow eye. They completed dry-eye questionnaires preoperatively and 1, 3, 6, and 12 months postoperatively. The effect of laser ablation depth, sex, age, and flap thickness on dry-eye symptoms was also analyzed.

The study enrolled 51 patients. There was no statistically significant change in dry-eye symptoms except in the femtosecond group 1 month postoperatively (mean increase 1.08) (P=.03). There were no significant differences in symptoms between the 2 groups (P=.7). The dry-eye score was 1.3 points lower in women than in men (P=.01). Central ablation depth, flap thickness, and age did not significantly affect the reported dryness.

There appeared to be no statistically significant difference in self-reported dry-eye symptoms between the mechanical keratome group and the femtosecond laser keratome group.

Neither author has a financial or proprietary interest in any material or method mentioned.

J Cataract Refract Surg. 2011 Jun 16. [Epub ahead of print]
Golas L, Manche EE.
From Stanford University School of Medicine, Stanford, California, USA.

Abstract: Veterans & dry eye

Some of the risk factors are typical (sleep apnea, because they're probably all using CPAP which is blowing in their eyes; thyroid disease has a known connection) but I find the connection with depression and PTSD quite interesting - I wonder if that really is as simple as antidepressant, antianxiety etc side effects or there is more to it. I tend to think that those conditions enhance eye pain in individuals who are not on medication.

Prevalence and Risk Factors of Dry Eye Syndrome in a United States Veterans Affairs Population.

To evaluate the prevalence of dry eye syndrome (DES) and its associated risk factors in a US Veterans Affairs population receiving ocular care services.

Retrospective study.

settings: Patients were seen in the Miami and Broward Veterans Affairs eye clinics between 2005 and 2010. patients population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD9 code for DES plus dry eye therapy; controls = patients without ICD9 code plus no therapy). Main outcome measures: The prevalence of DES and its associated risk factors.

A total of 16 862 patients were identified as either a dry eye case (n = 2056) or control (n = 14 806). Overall, 12% of male and 22% of female patients had a diagnosis of DES, with female gender imparting a 2.40 increased risk (95% confidence interval [CI] 2.04-2.81) over male gender. Several medical conditions were found to increase DES risk including post-traumatic stress disorder (odds ratio [OR] 1.97, 95% CI 1.75-2.23), depression (OR 1.91, 95% CI 1.73-2.10), thyroid disease (OR 1.81, 95% CI 1.46-2.26), and sleep apnea (OR 2.20, 95% CI 1.97-2.46) (all analyses adjusted for gender and age). The use of several systemic medications, including anti-depressant medications (OR 1.97, 95% CI 1.79-2.17), anti-anxiety medication (OR 1.74, 95% CI 1.58-1.91), and anti-benign prostatic hyperplasia medications (OR 1.68, 95% CI 1.51-1.86), was likewise associated with an increased risk of DES.

The prevalence of DES was found to be high in both men and women in our eye care population. This is the first study to demonstrate that in a veteran population, several diagnoses were significantly associated with DES, including post-traumatic stress disorder and depression.

Am J Ophthalmol. 2011 Jun 17. [Epub ahead of print]
Galor A, Feuer W, Lee DJ, Florez H, Carter D, Pouyeh B, Prunty WJ, Perez VL.
Bascom Palmer Eye Institute, University of Miami, Miami, Florida; Miami Veterans Administration Medical Center, Miami, Florida.

Abstract: Doxy 40mg for ocular rosacea

Nice results reported with doxycycline use in this study.

Treatment of ocular rosacea with 40 mg doxycycline in a slow release form.

About 30-50 % of rosacea patients have ocular involvement. The symptoms range from a foreign-body sensation to conjunctivitis or blepharitis and may even include severe corneal ulcerations. Systemic treatment is generally with tetracycline. Side effects can occur with the usual antimicrobial dose.

Patients and Methods:
In a retrospective study, seven patients were evaluated who had been treated for ocular rosacea with a sub-antimicrobial dose of doxycycline 40 mg in a slow-release form (Oraycea(®) ). The responses were evaluated on the basis of clinical findings.

Seven patients with an average age of 63 took slow release doxycycline 40 mg every day for at least two months. In five patients, other systemic drugs had already failed. All patients experienced a clear improvement in their ocular rosacea after an average of 2.29 months of treatment. One patient had complete clearance and another had almost complete clearance. None of the patients experienced side effects.

A sub-antimicrobial dose of slow release doxycycline 40 mg daily is an effective long-term therapy for ocular rosacea. It is not associated with the side effects of long-term antibiotic therapy or the risk of resistance.

J Dtsch Dermatol Ges. 2011 Jun 15. doi: 10.1111/j.1610-0387.2011.07723.x. [Epub ahead of print]
Pfeffer I, Borelli C, Zierhut M, Schaller M.
Department of Dermatology, Tübingen University Hospital, Germany Department of Ophthalmology, Tübingen University Hospital, Germany.

Abstract: The BAK battle - Xalatan vs Travatan Z

This is an interesting study attempting to capture incidence of new dry eye diagnoses potentially caused by glaucoma medication preservatives, but it's not a medical study - rather they analyzed a coding database to see if the new glaucoma med users were newly diagnosed with dry eye or were prescribed Restasis more frequently if using a BAK-preserved glaucoma drop or not.

The comparison was between Xalatan (with BAK) and the newer Travatan-Z (widely pushed as a BAK-free alternative). The results did not indicate that Travatan-Z performed better in the first year - however, that is not particularly surprising because unless the individuals already have dry eye, or have a sensitivity to BAK specifically, I don't think daily BAK would be expected to cause harm to a healthy cornea in such a short time anyway.

Incidence of new coding for dry eye and ocular infection in open-angle glaucoma and ocular hypertension patients treated with prostaglandin analogs: Retrospective analysis of three medical/pharmacy claims databases.

BMC Ophthalmol. 2011 Jun 14;11(1):14. [Epub ahead of print]
Schwartz GF, Kotak S, Mardekian J, Fain JM.

To investigate the clinical relevance of two different preservative formulations, we compared 1-year incidence rates of additional coding of dry eye, ocular infection, or ocular surface disease (either dry eye or ocular infection) in open-angle glaucoma and ocular hypertension patients newly treated with latanoprost with benzalkonium chloride (BAK) or with travoprost-Z with SofZia(R).

This was a retrospective study of three U.S.-based patient-centric medical/pharmacy claims databases (MedStat, PharMetrics, i3-Ingenix). Patients were eligible if they filled a prescription for latanoprost or travoprost-Z between October 2006 and Q2 2008 (prescription date=index date) AND were continuously enrolled 6 months prior through 12 months after the index date AND had any open-angle glaucoma or ocular hypertension diagnosis within 90 days prior to the index date AND did not have an ocular surface disease diagnosis during the 180 days prior to the index date AND if they had not had a prescription for the index agent in the 180 days prior to the index date. Time to incidence of new coding for ocular surface disease in the first year post-index was estimated with a composite endpoint: diagnosis of dry eye or ocular infection by ICD-9-CM or Current Procedural Terminology code OR by prescription for cyclosporine ophthalmic emulsion or ocular antibiotics.

In all, 15,933 patients were treated with latanoprost and 7670 with travoprost-Z. Over 1 year, 4.3% of latanoprost and 4.5% of travoprost-Z patients were identified with dry eye (p=0.28), and 10.9% and 11.1%, respectively, were identified with an ocular infection (p=0.79). The 1-year incidence of new coding for ocular surface disease also was similar across treatments (13.9% vs 14.3%, respectively; p=0.48).

The retrospective analysis of three large prescription databases revealed that open-angle glaucoma and ocular hypertension patients newly treated with latanoprost preserved with BAK or travoprost-Z preserved with SofZia did not differ statistically in rates of dry eye, ocular infection, or ocular surface disease (either dry eye or ocular infection) during the first year post-index. Claims-based analyses are limited by nonrandomization and the inability to account for over-the-counter use or samples.

Device news: Lipiflow

TearScience's Lipiflow is all the rage right now and for good reason. We have several people on the board who have undergone the procedure either in Europe, Canada or as part of a clinical trial in the US (where it is not yet approved) Thus far it is available in Toronto and in Abbotsford BC.

YouTube news video on Lipiflow at Herzig Eye in Toronto

June 9 press release:
TearScience Launches Breakthrough Technology in Canada to Address the Root Cause of Evaporative Dry Eye
TearScience Introduces LipiView® and LipiFlow® Devices at Canadian Ophthalmic Society Exhibition

MORRISVILE, N.C.--(BUSINESS WIRE)--TearScience, Inc., a privately-held medical device company, today announced the product launch of its LipiView® Ocular Surface Interferometer and LipiFlow® Thermal Pulsation medical devices in Canada. TearScience’s devices were designed to help eye care physicians address a root cause of evaporative dry eye, Meibomian Gland Dysfunction (MGD), which results in a lipid deficiency of the eye’s natural tear film. LipiView® helps physicians visualize the eye’s natural tear film. LipiFlow® is designed to alleviate meibomian gland obstructions by applying a precise combination of directed energy to eyelids during a 12 minute in-office treatment.

“Our goal is to help physicians make a meaningful difference for those who suffer from chronic evaporative dry eye.”
TearScience will demonstrate its devices at the Canadian Ophthalmic Society (COS) exhibition on June 9-12, 2011 at the Westin Bayshore Hotel in Vancouver at booth #28.

“TearScience is introducing a revolutionary technology as a new alternative to traditional treatments for Meibomian Gland Dysfunction,” said Jeff O’Hara, vice president of sales for TearScience. “Our goal is to help physicians make a meaningful difference for those who suffer from chronic evaporative dry eye.”

Herzig Eye Institute of Toronto is one of the first eye care practices in North America to implement TearScience’s system and has begun treating patients over the last several months.

Of the more than 100 million dry eye sufferers worldwide, approximately 65 percent have evaporative dry eye. Common symptoms of the disease include eye irritation, dryness, redness, tiredness, and visual disturbances.

In a randomized, controlled, multi-center clinical trial involving 139 patients, which compared the LipiFlow® System to iHeat™ warm compresses therapy for the treatment of Meibomian Gland Dysfunction, the total meibomian gland secretion score improved in 90 percent of patients at 4 weeks. Additionally, dry eye symptoms were improved from before the LipiFlow® treatment in 84-88 percent of patients at four weeks based on two different recognized symptom questionnaires, Standard Patient Evaluation of Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI).

TearScience will sell its LipiView® and LipiFlow® devices as a system to eye care practices. LipiView® recently won the Medical Design of Excellence Award from UBM Canon.

Abstract: Lacrimal gland prolapse in blepharoplasty

Thought this was kind of interesting given how many blepharoplasty patients we have in the dry eye crowd.

Prevalence of Lacrimal Gland Prolapse in the Functional Blepharoplasty Population.

Traditional functional blepharoplasty has focused on the excision of variable amounts of skin, muscle, and fat, with little attention given to the finding of the lacrimal gland prolapse (LGP). The reported incidence of LGP found on clinical examination, on patients of all ages presenting for blepharoplasty, is 15%. The author's experience with the procedure in the older age group (older than 60), is that this percentage is much lower than that found at surgery. To verify whether this is correct, the author evaluated lacrimal gland position intraoperatively in a group of patients undergoing functional upper blepharoplasty. In those patients who had LGP, the author routinely repositioned the gland and evaluated surgical outcomes.

The author evaluated the presence of an intraoperatively displaced lacrimal gland in his functional blepharoplasty population over a 2.5-year period (2008-2010). Patients with a history of previous eyelid surgery, trauma, or who had concurrent ptosis or other eyelid malpositions were excluded from the study. When present, the degree of prolapse was graded as mild (0-2 mm), moderate (3-5 mm), or severe (6 mm or more). The author arbitrarily suture-repositioned the gland in all patients with 4 mm or more of prolapse. In cases with less prolapse, light cautery to the tip of the gland capsule and surrounding soft tissue allowed adequate repositioning without suture fixation. Pertinent patient demographics and postoperative complications were documented. Patients were seen consistently to 6 months after surgery with an average follow up of 12 months.

Fifty-seven patients were included in the study. Thirty-four patients (60%) had some degree of LGP. Of these, 8 patients (24%) had mild prolapse, 23 patients (67%) had moderate prolapse, and 3 patients (9%) had severe prolapse. Nineteen patients (56%) with LGP had the gland suture-repositioned, and 15 patients (44%) received cautery to retro-place the gland. In one patient (3%), transient dry-eye symptoms developed after surgery. Otherwise, there were few benign and self-limiting postoperative complications, consisting of prolonged upper eyelid swelling and transient mild pain.

Lacrimal gland prolapse is a common finding during functional upper blepharoplasty surgery and appears to be a normal involutional periorbital aging change. Most cases are moderate in degree (as defined in the article), and not associated with specific preoperative symptoms or complaints, except lateral hooding with concomitant visual field deficit. Repositioning the gland intraoperatively is generally complication free and typically not associated with increased morbidity or healing time. The clinical significance of LGP in the elderly undergoing blepharoplasty surgery is unknown and requires further study.

Ophthal Plast Reconstr Surg. 2011 Jun 8. [Epub ahead of print]
Massry GG.
Ophthalmic Plastic and Reconstructive Surgery, Spalding Dr. Cosmetic Surgery and Dermatology, Beverly Hills, California, U.S.A.

Retaine MGD (Cationorm) coming to US/Canada

Dry Eye Therapy Utilizing Cationic Novasorb® Technology Available Soon From OCuSOFT®

RICHMOND, Texas, June 14, 2011 /PRNewswire/ -- OCuSOFT, Inc., an ophthalmic pharmaceutical research, development and supply company today announced an exclusive multiyear agreement with Ardeo Health, LLC to distribute a novel dry eye therapy under license from Novagali Pharma S.A. of Evry, France, Nova23041.

Nova23041 will be marketed and distributed in the United States and Canada as Retaine® MGD™ Ophthalmic Emulsion under a brand license from OCuSOFT, Inc. Utilizing Novagali's Novasorb® Technology—a proprietary cationic process of binding positively charged ions to the negatively charged ocular surface, Retaine® MGD™ will prolong corneal contact time resulting in enhanced comfort. As a preservative-free oil-in-water emulsion, Retaine® MGD™ will target individuals suffering from Meibomian Gland Dysfunction, a component of Dry Eye Syndrome.

Cynthia Barratt, President and CEO of OCuSOFT, Inc. comments, "OCuSOFT® has been searching for a truly unique proprietary Dry Eye therapy which also combines a long-term partnership—and we have found that with Ardeo Health and Novagali. I believe Retaine® MGD™ will become the standard of care for those suffering with Meibomian Gland deficiencies."
"Everyone at Ardeo Health is excited to see this newest technology brought to North America. Patients suffering from moderate to severe Dry Eye will now have an alternative to expensive prescription (Rx) therapies," states Robert "Bob" Sykora, RPh, President & CEO of Ardeo Health. "With these partnerships, Ardeo has the best of both worlds—the science of Novagali coupled with the brand recognition and distribution channels of OCuSOFT®."

Jerome Martinez, Chairman of Novagali Pharma, concludes "We are very pleased to be able to announce, today, the signing of this agreement involving two major American ophthalmology players. Given their proven expertise on the North American ophthalmology market, OCuSOFT®'s teams will no doubt make Nova23041's launch in the United States and Canada a success that will enable us to extend the distribution of our unique formulation for treating dry eye symptoms around the world. This agreement confirms the growing reputation of the products and technologies developed by Novagali Pharma in the United States."

Abstract: Trehalose

A sugar under investigation for a number of things including dry eye:

Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology.

Trehalose is a naturally occurring disaccharide comprised of two molecules of glucose. The sugar is widespread in many species of plants and animals, where its function appears to be to protect cells against desiccation, but is not found in mammals. Trehalose has the ability to protect cellular membranes and labile proteins against damage and denaturation as a result of desiccation and oxidative stress. Trehalose appears to be the most effective sugar for protection against desiccation. Although the exact mechanism by which trehalose protects labile macromolecules and lipid membranes is unknown, credible hypotheses do exist. As well as being used in large quantities in the food industry, trehalose is used in the biopharmaceutical preservation of labile protein drugs and in the cryopreservation of human cells. Trehalose is under investigation for a number of medical applications, including the treatment of Huntington's chorea and Alzheimer's disease. Recent studies have shown that trehalose can also prevent damage to mammalian eyes caused by desiccation and oxidative insult. These unique properties of trehalose have thus prompted its investigation as a component in treatment for dry eye syndrome. This interesting and unique disaccharide appears to have properties which may be exploited in ophthalmology and other disease states.

Clin Ophthalmol. 2011;5:577-81. Epub 2011 May 10.
Luyckx J, Baudouin C.
Thea Laboratories, Clermont-Ferrand.

Abstract: Lacrisert literature review

Review of hydroxypropyl cellulose ophthalmic inserts for treatment of dry eye.

Dry eye syndrome is a prevalent disease that affects visual acuity, activities of daily living, and quality of life. A number of contributory factors affect the severity of dry eye syndrome, including autoimmune disease, environmental surroundings, contact lens use, hormonal changes, anatomical features, chronic inflammation, infections, and iatrogenic factors, such as medications or surgery. Symptoms may include intermittent or constant blurry vision, discomfort, burning, foreign body sensation, hyperemia, dryness, and photophobia. The severity of dry eye syndrome can range from very mild disease to extremely severe cases with vision-threatening consequences. A variety of dry eye treatment modalities exist to address the different causes, symptoms, and consequences of ocular surface disease, including artificial tears, lubricating gels, ophthalmic inserts, anti-inflammatory drops, and surgical procedures. In this paper, an assortment of literature pertaining to the treatment of dry eye syndrome, in particular hydroxypropyl cellulose ophthalmic inserts, is reviewed. These inserts can be used effectively as monotherapy, or in conjunction with other therapies, and should be considered in the treatment of dry eye syndrome.

Clin Ophthalmol. 2011;5:587-91. Epub 2011 May 11.
Nguyen T, Latkany R.
Dry Center, Physician Eyecare of New York, New York, NY, USA.

Abstract: LIF accelerating corneal nerve regeneration after LASIK... bunnies, in the first five months. Very interesting.

Effect of leukemia inhibitory factor on corneal nerve regeneration of rabbit eyes after laser in situ keratomileusis.

To explore the effect of leukemia inhibitory factor on corneal nerve regeneration in a rabbit model after laser in situ keratomileusis. Thirty five healthy New Zealand rabbits were divided into three groups for a 6-month observation, the blank control group, the control group, and the treatment group respectively. Laser in situ keratomileusis for myopia was performed on 30 rabbits (60 eyes in total) and then 1μg/ml LIF eye drops were used four times a day on the left eyes as the treatment group, and the balanced salt solution (BSS) was used on the right eyes as the control group. Nerve regeneration was evaluated by counting the new regenerated nerves in golden chloride staining. The parameters for dry eye include Schirmer I test and tear break-up time were also examined. The number of regenerated nerve fibers in the treatment group was significantly higher than that in the control group at all time points except the 6th month after LASIK (P < 0.05). The parameters for dry eye between two groups were compared at each postoperative time point and the results showed they were significantly higher in the LIF-treated group than in the BSS-control group at 2w, 1m, and 3m respectively. Leukemia inhibitory factor can effectively accelerate the corneal nerve regeneration of rabbit eyes after LASIK surgery and decrease the occurrence of dry eye symptoms.

Neurosci Lett. 2011 Jul 20;499(2):99-103. Epub 2011 May 26.
Pan S, Li L, Xu Z, Zhao J.
Ophthalmology Center, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Abstract: Typical dry eye testing in Spain

Knowledge and Use of Tear Film Evaluation Tests by Spanish Practitioners.

The present study aimed at investigating the use and knowledge of tear film and dry eye evaluation tests by a representative sample of Spanish optometrists and ophthalmologists.

A simple on-line survey was designed to explore the preferred tests for tear film evaluation and dry eye diagnosis. Additional questions surveyed knowledge of basic tear film evaluation concepts, attitude (proactive or reactive) toward patient symptoms and use of standardized dry eye questionnaires. Respondents also provided information regarding academic background, continuing education and training courses, and weekly number of tear film examinations.

A total of 140 optometrists and 103 ophthalmologists responded to the survey. The tear break-up time test was the first preference of optometrists and ophthalmologists, whereas the Schirmer test and the non-invasive break-up time were frequently reported by ophthalmologists and optometrists, respectively, to supplement a first test. Optometrists and ophthalmologists were similar in terms of continuing education, knowledge of basic tear film concepts, and attitude regarding symptoms. Continuing education was found to positively influence knowledge, attitude toward symptoms and use of more sophisticated tear film evaluation tests. Standardized dry eye questionnaires were rarely used. A strong positive statistically significant correlation was encountered between the number of continuing education and training courses and the number of weekly tear film examinations.

Continuing education is an invaluable tool for practitioners to increase their self-confidence and improve their clinical practice when conducting tear film evaluations and dry eye diagnosis.

Optom Vis Sci. 2011 Jun 2. [Epub ahead of print]
Cardona G, Serés C, Quevedo L, Augé M.
*PhD †MSc University Vision Centre, Universitat Politècnica de Catalunya, Terrassa, Spain.