Friday, April 16, 2010

Drug news: Japan approves Prolacria sibling from Inspire

Japan approves dry-eye drug from Inspire, Santen

A stronger version of a dry eye drug stymied by regulatory roadblocks in the United States has won approval for sale in Japan, Durham-based Inspire Pharmaceuticals announced Friday.

Inspire (Nasdaq: ISPH) and its partner on the drug, Japan-based Santen Pharmaceutical Co., Ltd., said in a joint news release that the Japanese Ministry of Health, Labour and Welfare gave the companies the green light Thursday to begin sales of Diquas Ophthalmic Solution 3%.

Diquas has the same active ingredient, diquafosol tetrasodium, as the Inspire drug Prolacria, which twice has failed to perform better than placebo in phase III clinical trials in the United States.

Clinical studies in Japan found that Diquas eased dry-eye symptoms by promoting the secretion of mucin and water. The drug also was found to be well tolerated in patients.

The drug that passed muster in Japan is different from Prolacria in two major ways, said Inspire spokeswoman Cara Amoroso. No. 1, Prolacria was a 2 percent diquafosol solution; Diquas is 3 percent. No. 2: Patients in the last Prolacria trial received four doses a day; patients in the Japanese tests used the eye drops six times a day.

Inspire is unlikely to pursue Food and Drug Administration approval of Diquas, with its higher concentration and dosaging, Amoroso said.

Thursday, April 15, 2010

Abstract: Schirmer (again)

After looking at 1-minute vs. 5-minute in Tehran, now we get 2-minute vs. 5-minute in Thessaloniki.

Personally, I don't really see the point of unanesthetized Schirmer. If they're THAT dry, isn't it pretty obvious? Are you guys also checking with anaesthesia?

Comparison Between Normal Values of 2- and 5-Minute Schirmer Test Without Anesthesia.
Cornea. 2010 Mar 17. [Epub ahead of print]
Karampatakis V, Karamitsos A, Skriapa A, Pastiadis G.
From the *Laboratory of Experimental Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

PURPOSE:: To compare the 2- and 5-minute Schirmer test I (test without anesthesia) in healthy individuals so as to exploit the possibility of using the 2-minute instead of the 5-minute test.

MATERIAL AND METHOD:: 162 healthy (81 males and 81 females) individuals (without dry eye symptoms and free of pathology affecting tear secretion and tear drainage), aged between 20 and 85, were recruited in the study (3 age-groups: 20-45, 46-65, and 66-85 years). Schirmer test I (test without topical anesthesia) was performed in both eyes simultaneously. The values of tear secretion were recorded in 2 and 5 minutes and compared in relation to age and gender. The patients were asked to comment on the duration and the discomfort they felt.

RESULTS:: In 2 minutes, the average tear secretion was 12.71 +/- 2.47 mm (mean +/- SD) for the right eyes and 12.62 +/- 2.09 mm for the left eyes and in 5 minutes, 16.74 +/- 3.59 and 16.831 +/- 3.38 mm, respectively. For confidence interval of 99%, the mean values of tear secretion, in individuals who were expected to have normal secretion, were higher than 10 mm in 2 minutes and higher than 13 mm in 5 minutes (significance level 1% or a = 0.01). Only 5.55% of the eyes presented values <10 mm (7-9.5 mm) in the 2-minute test and values <13 mm (8.5-12.5 mm) in the 5-minute test. There was no significant difference in tear secretion between males and females, between the different age-groups, and between right and left eyes. All the examined individuals expressed their negative comments and considered the test as an unpleasant procedure and consequently preferred the shorter possible duration.

CONCLUSION:: The 2-minute test is more acceptable by both the examiners and the examined individuals and may be used, in respect to the above results, as an alternative of the 5-minute test. Normal individuals tend to have Schirmer test I values >/=10 mm in 2 minutes, irrespective of age and gender.

Abstract: Systane after cat surgery

The effect of preservative-free HP-Guar on dry eye after phacoemulsification: a flow cytometric study.
Eye (Lond). 2010 Mar 19. [Epub ahead of print]
Sánchez MA, Arriola-Villalobos P, Torralbo-Jiménez P, Girón N, de la Heras B, Herrero Vanrell R, Alvarez-Barrientos A, Benítez-Del-Castillo JM.
Department of Ophthalmology, Hospital Clínico San Carlos, Madrid, Spain.

To assess the effect of hydroxypropyl (HP)-Guar added to regular post-phacoemulsification treatment in dry eye signs and symptoms, and its influence on the expression of various inflammatory markers by flow cytometry (FCM) in impression cytology specimens.
This prospective, interventional, single-centre study included 48 eyes of 48 patients with age-related cataract. After phacoemulsification, patients were randomised to the usual treatment group (UT), with 21 patients who received tobramycin and dexamethasone eye drops (Tobradex, Alcon Cusí, Spain), and the HP-Guar group, with 27 patients who received the UT plus preservative-free artificial tears (Systane UD, Alcon Cusí, Spain). Corneal and conjunctival staining with fluorescein and lissamine green, tear film break-up time (TBUT), Schirmer's I test with anaesthesia (Jones test), tear clearance, and ocular surface disease index (OSDI) were assessed preoperatively and 1 month after surgery. Besides, conjunctival impression cytology was performed in order to investigate inflammatory markers (CD3, CD11b, and HLA-DR) using FCM.
HP-Guar group shows statistical better results compared with the UT group in TBUT (6.4+/-0.7 vs9+/-2.5, P=0.0004), OSDI (11.5+/-8.2 vs3.3+/-2.5, P=0.0002), ocular symptoms subscale (7.3+/-6.1 vs1.7+/-1.8, P=0.0004), vision-related function subscale (2.2+/-1.8 vs0.4+/-0.6, P=0.0002), CD3 (2.5+/-1.4 vs1.1+/-1.1, P=0.011), and HLA-DR (6.8+/-4.5 vs1.8+/-1.7, P=0.0002).
The addition of HP-Guar to regular treatment after cataract surgery reduces ocular surface inflammation and dry eye signs and symptoms.

Abstract: Ummm.

An autoimmune response to odorant binding protein 1a is associated with dry eye in the aire-deficient mouse.
J Immunol. 2010 Apr 15;184(8):4236-46. Epub 2010 Mar 17.
DeVoss JJ, LeClair NP, Hou Y, Grewal NK, Johannes KP, Lu W, Yang T, Meagher C, Fong L, Strauss EC, Anderson MS.
Diabetes Center, University of California-San Francisco, San Francisco, CA 94143, USA.

Sjögren's Syndrome (SS) is a human autoimmune disease characterized by immune-mediated destruction of the lacrimal and salivary glands. In this study, we show that the Aire-deficient mouse represents a new tool to investigate autoimmune dacryoadenitis and keratoconjunctivitis sicca, features of SS. Previous work in the Aire-deficient mouse suggested a role for alpha-fodrin, a ubiquitous Ag, in the disease process. Using an unbiased biochemical approach, however, we have identified a novel lacrimal gland autoantigen, odorant binding protein 1a, targeted by the autoimmune response. This novel autoantigen is expressed in the thymus in an Aire-dependent manner. The results from our study suggest that defects in central tolerance may contribute to SS and provide a new and clinically relevant model to investigate the pathogenic mechanisms in lacrimal gland autoimmunity and associated ocular surface sequelae

Abstract: A month of Optive vs. Hylocomod

Ho hum.

Evaluation of the effects on conjunctival tissues of Optive eyedrops over one month usage.
Cont Lens Anterior Eye. 2010 Apr;33(2):93-9.
Guillon M, Maissa C, Ho S.
OTG Research & Consultancy, London, UK.

The objective was to compare the effect on conjunctival tissues of the repeated use, over a one-month period, of Optive compared to Hylocomod eyedrops by a population of dry eye sufferers. The rationale for the study was that among dry eye sufferers who attend eye care practices for symptomatic relief, a large number present with conjunctival anomalies evidenced by tissue staining and that conjunctival recovery is essential to their successful long term management. The hypothesis tested was that the decrease in conjunctival staining with Optive is at least as good, and possibly greater, than that with Hylocomod. The cohort population was made up of 47 subjects (11 male and 26 female) aged 42+/-16 years with at least mild dry eye symptoms and conjunctival and/or corneal staining. The population included contact lens wearers (n=26) and non-wearers (n=21). The subjects were randomly allocated to use one of the two study products; they were instructed to use the products as often as needed but at least three times a day. Conjunctival staining was rated on forced choice scales and measured objectively using digital photographs and image analysis. The findings showed that, whereas the staining at the start of the investigation was similar (p=0.318-0.664), staining after one month of use was significantly less with Optive than Hylocomod (p=0.028-0.002). The results demonstrated that the regular use of Optive over one month was significantly superior to Hylocomod in improving conjunctival status by producing a greater reduction in the staining of dry eye sufferers. 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Drug news: Prolacria (via Santen Pharma)

Well, it died in the US, but financial projections indicate it's expected to hit the Japanese market (huge dry eye market, by the way) in the third quarter of 2011. It's listed as DE-089.

Newsblurb: A Korean journalist gets LASIK

I usually glance through these things and delete them. This one arrested my attention. It's an interesting and candid story of a journalist undergoing LASIK to find out what it was like. - I wish Abby Elin had had a similar outcome - sigh. On the other hand, this journalist is only 5 weeks out and I wonder where she'll be in dry eye tears a year hence.

Finally... I was really tickled at the - perhaps - unwittingly apt use of the term 'refractory surgery' rather than 'refractive surgery'.

Pains, Gains, Perils of Laser Eye Surgery

Corrective laser eye surgeries have become quite common in South Korea over the past decade but many are still concerned about the safety of such operations. After weeks of searching the Internet and asking for advice, this reporter, with poor vision in both eyes, decided to give it a try and see how it really works out.

Among hundreds of eye clinics in Seoul, I chose one of the busiest. The BGN Eye Clinic, near Gangnam Station, where eye and cosmetic surgeons are operating is in a kind of industrial cluster. It was also one of most heavily advertised on the Internet, and its prices looked higher than average....

An optometrist greeted me at the door. Young and immaculately dressed, he spoke in the manner of an insurance salesman rather than a medical worker. He seemed knowledgeable about all kinds of eye surgeries, fielding my tricky questions confidently.

His attitude was contagious. After two hours of consultation and check-ups, I was convinced that I wouldn't be one of the tiny, unfortunate minority of patients who suffer side effects after surgery....

``You can opt for the blade type if you are really concerned about price,'' he said, though his lecture so far had scared me enough that I didn't want to downgrade myself to steel from laser only to save some money. (Later, I learned that many surgeons in the United States still prefer the blade operation because it is quicker and therefore less harrowing to most patients.)

Then we talked about price. Refractory operations, like cosmetic surgery, are not covered by medical insurance in Korea. The optometrist asked for 2.6 million won ($2,250) for both eyes, which was about double the rate of smaller clinics. I said that was beyond my budget. The price immediately went down to 2.3 million won.

Then he made a curious offer ― if I promised to write a review of my operation on the clinic's Web site, he would give me a further 100,000-won reduction. I turned down the offer, but anyway, the ``discount'' was granted.

The bill included the cost of the operation and eye checkups but not medicine, which cost another 30,000 won....

ith my eyeball exposed widely liked an orange peeled halfway, I could feel the doctor put some kind of metal ring on it. As he muttered "suction," the eye was sucked into the vacuum hose and held tight inside it. This was a very uncomfortable sensation. A waterfall of tears ran down. A second felt like a year.

Once the eyeball was anchored on the vacuum hose, the rest of the operation was relatively easy. The nurse counted to 15 while the laser sliced the skin of the cornea to make a flap. Then another laser beam hit the inside the flap to remove excessive tissues of the cornea. I could see nothing but flashing lights of red and orange, but there was a faint smell of burning flesh. After a minute or so, the doctor closed the flap into its original place so it can heal with the rest of the cornea.

The operation on the right eye took no more than five minutes but I was already exhausted by then. The same procedure went on for the left eye. This time, the suction hose failed to suck my eyeball correctly two times, making me very uneasy....

From the next morning, I could see things quite clearly. I returned to work the second day after the operation. The vision improved week by week until it reached 1.0 a month after, equivalent to 20/20 in America, and considered the average of people with healthy eyes....

Five weeks have passed and there have been no serious side effects apart from the occasional dryness of the eyes. But I'm not at ease yet. One of my cousins had LASIK a few years ago and she had to have a further operation a year after the first one. Her doctor said it was because she had a keloidal skin, which is allergic to scars and can affect the healing process of the wound. I, too, have had this problem before. My optometrist at BGN clinic said this doesn't cause trouble, usually....

Lifestyle and career can also be an important issue when considering refractory operations. It is no secret that eye surgeons themselves prefer wearing glasses or contact lenses to surgery, because their job requires reliable and acute vision. Even my surgeon at BGN was wearing glasses when I saw him outside the hospital. After all, the risk is for the patients to take.

Abstract: Yeah, we know, women over 45...

Tear film dynamics and lipid layer characteristics-Effect of age and gender.
Cont Lens Anterior Eye. 2010 Mar 2. [Epub ahead of print]
Maïssa C, Guillon M.
OTG Research & Consultancy, London, UK.

PURPOSE: Dry eye disease is significantly more prevalent in older subjects and among them more marked in women than men. Further, it is established that the tear film dynamics of dry eye sufferers is different to that of normal. It is therefore postulated that the greater prevalence of dry eye problems with advancing age is at least in part related to poorer tear film dynamics.

METHODS: Tear film dynamics (non-invasive break up time) and lipid characteristics (lipid layer thickness and contamination) were assessed using the Tearscope lighting system.

RESULTS: 160 Subjects less than 45 years old and 58 subjects aged 45 years or more formed the study populations. The tear film stability was mostly influenced by age; the break up time was statistically significantly shorter for the older age group (p<0.001). The lipid layer was also significantly thinner (p=0.013) for the subjects aged 45 years or older with a very marked synergic effect of age and gender. The lipid layer of older women was significantly thinner and more contaminated than that of younger women (p=0.002 and <0.001) and of older men (p=0.034 and 0.004).

CONCLUSIONS: Aging of the tear film is characterised by its destabilisation associated with significant changes in the tear lipid layer producing less protection from evaporation in the older population; the observed changes are more marked in women than in men. The findings have significant implications for the management of presbyopic dry eye sufferers, for whom decreasing evaporative problems is essential.

Abstract: Omega 3s and corneal nerve regeneration after refractive surgery

Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgery.
Prostaglandins Leukot Essent Fatty Acids. 2010 Mar 2. [Epub ahead of print]
He J, Bazan HE.
Department of Ophthalmology and Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Dry eye (DE) is a multifactorial condition that affects the surface of the eye and induces an inflammatory response. Corneal nerves play an important role in the maintenance of a healthy ocular surface. Here we review corneal structure, nerve architecture, DE conditions, and nerve regeneration following corneal surgery and discuss how n-3 fatty acids affect the health of the cornea. Animal studies show that resolvins, compounds derived from eicosapentaenoic acid (EPA), increase tear volume and decrease inflammation induced by DE. After corneal surgery in rabbits, treatment with nerve growth factor (NGF) or pigment epithelial derived factor (PEDF) in conjunction with docosahexaenoic acid (DHA) increase nerve density and corneal epithelial cell proliferation. Increased synthesis of the novel docosanoid, neuroprotectin D1 (NPD1), was found in corneas after the animals were treated with PEDF and DHA. Topical application of these lipids derived from n-3 fatty acids could be useful in treating DE and prevent clinical complications such as cornea erosion and ulcerations.

Newsblurb: Dry eye in the military

This is the first time I recall seeing an article draw attention to the higher risk of dry eye in the military:

Military members susceptible to dry eye syndrome
March 5, 2010
The Fort Leavenworth Lamp

ABERDEEN PROVING GROUND, Md. - Have you experienced a stinging, burning or scratchy sensation in your eyes? Have you ever had stringy mucus in or around your eyes, increased eye irritation from smoke or wind, eye fatigue after short periods of reading? Perhaps you've noticed light sensitivity, tearing, blurred vision or a sense that a foreign substance is in your eyes.

If so, you may have dry eyes.

Dry eye syndrome is a common disorder that affects a large part of the population, mostly women and those over age 40. However, because of environmental conditions at military installations and deployment locations, service members may also be at risk for DES.

This condition results when there is an imbalance in the tear system. Tears are a mixture of saltwater, fatty oils and mucus. Together these three layers form a film that lubricates the eyes between blinks, resulting in comfortable and clear vision. When these three layers are not performing properly, dry eyes may result. Decreased production of fluids from tear glands can destabilize the tear film, allowing it to break down and create dry spots on the surface of the eyes.

Dry eyes can also occur when individuals cannot produce enough tears to keep their eyes lubricated or when there is excessive tear evaporation. Other factors that have been associated with dry eyes are adverse reactions to medications such as antidepressants, antihistamines and oral contraceptives. Exposure to environmental conditions that have a drying effect can also increase the risk for dry eyes.

Although no cure exists for DES, many treatments are available. Seek medical advice for prolonged symptoms, such as red, itchy, tired and painful eyes.

If DES is diagnosed, your health care provider may use artificial tear drops, ointments, silicone plugs, prescription eye drops or other medications to alleviate the symptoms...