Friday, December 19, 2008


Welcome to Kitsap County, in the famed temperate climate of the Pacific Northwest.

It's 8pm, 18 degrees Farenheit and dropping.

The latest weather forecast from Komo suggests our snowfall tomorrow night into Sunday is probably going to be measureable in feet. And there is something in how they're phrasing it all that just sounds ominously different than those notorious Seattle attempts at forecasting snow that never materializes.


Something tells me The Dry Eye Shop may not be open for business Monday. I will do my best to get the latest orders packed up and out tomorrow morning for those who may need them before Christmas.

Drug co. news: Inspire lawsuit dismissed

Remember when the FDA said no to Diquafosol for the third time and shareholders got unhappy...?

Inspire have now been vindicated with a Federal court dismissal of the class-action suit.

Federal court dismisses class-action suit against Inspire Pharmaceuticals

Management at Inspire Pharmaceuticals could have one less issue on its plate now that a federal court of appeals has moved to dismiss a class-action suit against the company.

The main claim in the class-action suit against Inspire Pharmaceuticals (Nasdaq: ISPH) is that executives at the Durham company committed securities fraud by overstating the prospects for an experimental dry-eye drug known as diquafosol tetrasodium. That drug failed a late-stage human trial, causing Inspire’s stock to drop more than 40 percent.

But on Dec. 12, the U.S. Court of Appeals for the Fourth Circuit, based in Richmond, Va., ruled that the suit should be dismissed. The plaintiffs didn’t offer enough evidence that Inspire’s executives willfully misled investors about studies of diquafosol tetrasodium, the court says. Rather, the court says, it seems clear that Inspire withheld the information for competitive purposes – a legitimate business purpose.

Thursday, December 18, 2008

winter wonderland and heating woes

I'll try and get a pic uploaded later today. It is SO beautiful here. We're having some very un-Puget-Sound-like winter weather in Poulsbo.

We had about 3" of snow on Saturday, and then it got quite cold... now it's snowing again and we've got a fresh inch or two. We missed the heavy snowfalls of 1-2' that blanketed some areas in Washington, but so much the better, especially given the state of the treads on my tires.

I think I've mentioned that this old farmhouse we've moved to has a wood-burning furnace. It's a bit of work, but I really welcome the exercise dealing with the firewood, and it really pumps out heat. There are ceiling vents downstairs and floor vents upstairs.

However, not too long after we moved in, the fan on the furnace came to a screeching halt. The local heating company (very nice people) took it away and managed to coax it back into some semblance of working order the very day before the temps dipped into the teens.

Only... where the fan was truly blowing before, it now seems to be just kind of reluctantly exhaling. When I found the bedroom not rising about 50 degrees, I called the heating company, who, of course, had about 150 other calls to handle from panicky locals and the last thing they were interested in was an ancient system for which they knew they could not find parts.

So I kept playing around with it, and finally found that if I really stuffed the furnace full and fed it frequently, I could get almost the entire upstairs to a reasonable temperature.

Now this is no small wood-burning stove - it holds quite a bit of wood. So I also let the property manager know that my budget was not anticipating burning a cord of wood a week through the winter and would she pretty please be so kind as to... do something. Word has it the heating company is going to rebuild the motor for me. Sometime. Meantime, it's now a balmy 26 degrees outside and most of the house except my office! is warming nicely. I never before had the opportunity to learn so much about the difference between teens and twenty-something.

Tuesday, December 16, 2008

Newsblurb: Allergan infomercial

Many Women Unaware Of Differences In Common Over-The-Counter Eye Drops

Gee, personally, I woulda said many women are aware of similarities in common over-the-counter eye drops (e.g. they don't work?).

Selecting eye drops can be an overwhelming experience with many different types and brands of over-the-counter eye drops on the market.

Got that part right.

The Red Hot Mamas® and Allergan, Inc., a global leader in eye care, recently conducted a nationwide survey of 371 women ages 45 to 65 who regularly experience at least one symptom of dry eye, and found that two-thirds of women experiencing dry eye symptoms were not aware of any difference between two common types of over-the-counter eye drops that are designed with different purposes-vasoconstrictors and artificial tears.

Got that part right too.

And your competitors over at Pfizer are probably 98% to blame for this by marketing BOTH artificial tears AND vasoconstrictors under the same label (the big V). I have ALWAYS felt that that was an unconscionable move... selling more by creating massive confusion. I haven't looked at the Visine line in awhile but when I last updated the site, there were 9 Visine products, 6 of which contained benzalkonium chloride and therefore are unsuitable for frequent use.

While approximately 20 million people in the United States have experienced dry eye symptoms, a medical condition called chronic dry eye often affects women because of hormonal changes due to aging and menopause. Other causes of dry eye include inflammation, certain medications and various systemic conditions.

You forgot to mention LASIK. If I'm not mistaken, considerably more people in this country have undergone LASIK than suffer from Sjogrens Syndrome, yet somehow, this is always left off the lists in any context in which it might, er, offend someone.

"We encourage women to focus on feeling good about menopause by taking personal control and gathering information during this natural transition," said Karen Giblin, president of Red Hot Mamas, the nation's largest menopause management education organization. "To that end, we are concentrating our efforts on raising awareness of dry eye, an often overlooked consequence of menopause."

I'm thrilled to hear it, and I sure hope your OTHER efforts are not as demeaning as that (shudder) Dry Eye Book Club thing.

"Artificial tears can provide temporary relief of dry eye symptoms, but they do not treat the underlying causes of chronic dry eye. Anyone experiencing the symptoms of dry eye or using artificial tears several times a day or on a regular basis should visit an eye doctor immediately, instead of continuing to try different over-the-counter artificial tears on their own," said Frank A. Bucci Jr., MD, founder and medical director of Bucci Cataract and Laser Vision Institute in Wilkes-Barre, PA. "An eye doctor can diagnose chronic dry eye and may recommend adding a prescription therapy."

Golly gee, that wouldn't be a gentle reference to Restasis, now, would it? (wink)

Monday, December 15, 2008

You mean....?

I got to the end of my list of updates. 25 posts, and a lot more reading of non newsworthy stuff. Un-friggin-believable - I get to finally cross this off my list. I think that is probably the most I've ever done in a single day. What a relief to finally be caught up.


Now, I turn to all the other things where I have equally long lists. Never mind, one at a time, they'll get done. If I ignored your email, forgive me, and call 877-693-7939 (I really do usually call back the same day whenever possible).

Abstract: Ooooh, real science

Judging from the title, anyway.

Modulation of integrin alpha4beta1 (VLA-4) in dry eye disease.
Arch Ophthalmol. 2008 Dec;126(12):1695-9
Ecoiffier T, El Annan J, Rashid S, Schaumberg D, Dana R

OBJECTIVE: To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti-VLA-4 sm) in a mouse model of dry eye disease.

METHODS: Anti-VLA-4 sm (or control vehicle) was applied topically to mice placed in a controlled-environment chamber. Corneal fluorescein staining and conjunctival T-cell enumeration were performed in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva.

RESULTS: Dry eye syndrome induced increased corneal fluorescein staining, corneal and conjunctival tumor necrosis factor alpha messenger RNA expression, and T-cell infiltration into the conjunctiva. Very late antigen 4 blockade significantly decreased corneal fluorescein staining compared with the untreated dry eye disease and control vehicle-treated groups (P < .001 and P = .02, respectively). In addition, VLA-4 blockade was associated with a significant decrease in conjunctival T-cell numbers (P < .001 vs control vehicle-treated group) and tumor necrosis factor-alpha transcript levels in the cornea (P = .04 vs control vehicle-treated group) and conjunctiva (P = .048 vs control vehicle-treated group).

CONCLUSION: Application of topical anti-VLA-4 sm led to a significant decrease in dry eye signs and suppression of inflammatory changes at the cellular and molecular levels.

CLINICAL RELEVANCE: Topical blockade of VLA-4 may be a novel therapeutic approach to treat the clinical signs and inflammatory changes accompanying dry eye disease.

Headline: Don't move to Tucson?!

OK so it wasn't exactly a headline, but this blurb from a newspiece on eye health made me chuckle for a moment when I thought of non-Tucsonians' reaction:

Living here can increase the risk of afflictions such as dry eye syndrome, which can cause stinging, burning, pain and redness in the eye.

Full article:
Keeping eyes healthy latest topic at science center

Newsblurb: Eyelash lengthening stuff by Allergan

Just a little heads up (again) about this. I think that people with dry eye are probably especially likely to consider ways to enhance their eye appearance that don't involve makeup... so beware that this could actually make your dry eyes worse.

UPDATE 2-Allergan drug lengthens eyelashes -US FDA staff

A drug from Botox maker Allergan Inc (AGN.N: Quote, Profile, Research, Stock Buzz) increased the length, thickness and darkness of eyelashes in a company study, U.S. drug reviewers said in a report released on Wednesday.

The analysis was prepared for a Food and Drug Administration advisory panel that meets Friday to evaluate the proposed cosmetic use of the drug, bimatoprost, now sold for treating glaucoma.

The panel of outside experts will consider if bimatoprost offers enough benefit to outweigh the risks of its use on the eyelashes, the FDA staff report said.

Four out of 137 patients who used the drug, which was applied daily along the upper eyelids, dropped out of Allergan's study because of mild or moderate eczema, dry eye, eye inflammation or dermatitis, FDA staff said.

Allergan, in a separate summary, said problems reported by users "occurred at a low frequency and were largely mild in severity, cosmetic in nature, and reversible." They included eye itchiness reported by 3.6 percent of patients, and eye irritation reported by about 2 percent of patients.

Gee, Allergan, I don't remember dry eye being cosmetic in nature.

Abstract: Intralase and dry eye

Typical. For FDA clinicals, of course we have to check both signs and symptoms because it is WELL KNOWN that there is a poor correlation between the two, but heaven forbid that anyone include assessment of symptoms in post refractive patients if they don't have to. JRS is probably the last ophthalmic publication I would expect to care about the distinction.

PURPOSE: To evaluate changes in comeal sensitivity and tear function following myopic LASIK with thin femtosecond flaps.
J Refract Surg. 2008 Nov;24(9):897-902
Barequet IS, Hirsh A, Levinger S.

METHODS: A retrospective study was performed to compare corneal sensitivity (filament), tear breakup time, and anesthetized Schirmer test preoperatively and at 1 week and 2 and 6 months postoperatively.

RESULTS: Seventy-two eyes of 38 consecutive patients (20 women and 18 men) who underwent LASIK for myopia or myopic astigmatism with thin femtosecond flaps (IntraLase femtosecond laser system and Technolas 217 PlanoScan V2.9992 or wavefront-guided Zyoptix 3.1 excimer laser) were evaluated. Preoperative mean corneal sensitivity was 5.3+/-1.5 mm, which decreased to 4.6+/-1.7 mm at 1 week, increased to 5.0+/-1.3 mm at 2 months, and returned to baseline values at 6 months postoperatively. Mean Schirmer score was 13.7+/-5.7 mm preoperatively and 12.1+/-5.1, 13.1+/-4.8, and 13.0+/-5.1 mm at 1 week and 2 and 6 months postoperatively, respectively. Mean tear breakup time was 7.7+/-2.6 seconds preoperatively and 7.8+/-3.5, 9.2+/-4.6, and 8.8+/-4.5 seconds at 1 week and 2 and 6 months postoperatively, respectively. No significant increase in fluorescein staining was observed throughout follow-up.

CONCLUSIONS: Reductions in corneal sensitivity and tear function tests were minimal after myopic LASIK with thin femtosecond flaps. Despite the relatively narrow hinge, the thin, uniform femtosecond flap does not appear to have an adverse effect on corneal sensitivity and dry eye signs at 6 months postoperatively.

Abstract: Radiation therapy for eyelid/conjunctiva cancers

The main reason this caught my eye was the remark in the conclusions that "the ocular side effects were relatively minor in most patients". That kind of thing always makes me wonder how they measured it, and whether the patients considered it minor.

Postoperative adjuvant external-beam radiation therapy for cancers of the eyelid and conjunctiva.
Ophthal Plast Reconstr Surg. 2008 Nov-Dec;24(6):444-9
Hsu A, Frank SJ, Ballo MT, Garden AS, Morrison WH, Rosenthal DI, Hatef E, Esmaeli B

PURPOSE: To outline the indications for and our experience with postoperative adjuvant external-beam radiotherapy (EBRT) in patients with eyelid or conjunctival cancers.

METHODS: Twenty consecutive patients with primary eyelid or conjunctival cancer treated with surgical resection followed by postoperative EBRT between January 2000 and September 2006 were included. The indications for postoperative EBRT, type and dose of EBRT, oculoplastic reconstructive procedures, timing of EBRT in relation to reconstructive procedures, and the ocular side effects of EBRT were recorded.

RESULTS: Sixteen women and 4 men ranged in age from 44 to 86 years (median, 64 years). The oculoplastic procedures included local flaps or direct closure of eyelid defect (12), tarsoconjunctival flap (6), full-thickness skin grafts (6), amniotic membrane grafts (2), other conjunctival reconstruction (2), tarsoconjunctival graft (1), and lacrimal stenting (1). The total radiation dose ranged from 26 to 63 Gy (median, 60 Gy). The indications for postoperative EBRT included aggressive histology, recurrent tumor, microscopic perineural invasion, advanced-stage disease, and microscopically positive or "close" margins. EBRT started 5 to 12 weeks (median, 7 weeks) after reconstructive procedures. The follow-up time ranged from 7 to 50 months (mean, 24 months). Thirteen patients experienced dry eye syndrome; 3 keratinization of conjunctiva; and 1 each blepharitis, trichiasis, radiation retinopathy/optic neuropathy, and exposure keratopathy.

CONCLUSIONS: Postoperative EBRT can be used as adjuvant therapy after surgical resection of eyelid or conjunctival cancers and may obviate more radical surgery such as orbital exenteration in some patients. The ocular side effects from EBRT were relatively minor in most patients.

Abstract: Varying the osmolarity of HLA

Compares hypotonic with isotonic HLA drops...

Bottom line, the hypotonic version felt better.
Cornea. 2008 Dec;27(10):1126-30
Troiano P, Monaco G.

Effect of hypotonic 0.4% hyaluronic acid drops in dry eye patients: a cross-over study.

PURPOSE: The aim of the study is to evaluate the short-term effects of 2 kinds of artificial tears, both containing 0.4% hyaluronic acid in an aqueous solution yet having different osmolarity, on the typical symptoms of patients suffering from dry eye and on the vitality of corneal and conjunctival epithelial cells.

METHODS: A cross-over, randomized, balanced, single-blind study involving 28 patients was divided into 2 treatment groups: group A (unpreserved 0.4% hyaluronic acid eye drops 300 mOsm/L) and group B (unpreserved 0.4% hyaluronic acid eye drops 150 mOsm/L). Both treatments were administered for 7 days, being dosed as a 1 solution drop 4 times daily. After a 1-day wash-out period, the patients in group A passed over to group B and vice versa.

RESULTS: Treatment with hypotonic solution gave better results in relieving symptoms, along with a statistically significant improvement (P < 0.001) in the state of the corneoconjunctival epithelium, than the isotonic solution. At the end of the study, 60.7% of the patients declared that they preferred hypotonic solution and only 10.7% preferred isotonic solution; the remaining 28.6% did not notice any difference between the 2 treatments.

CONCLUSIONS: By reducing the osmolarity of tear film, the hypotonic solution not only improves the characteristics of tear film and the vitality of the epithelial cells of the cornea and conjunctiva but also proves to be effective in reducing dry eye symptoms.

Abstract: MG diagnostics

Nice one. Presumably partly driven by a plug (no pun intended, single or double) for an MG paddle but all the same, I like seeing anything out there that will help get doctors hands-on with their patients' eyelids and also help them know what the heck to look for.

Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location.
Cornea. 2008 Dec;27(10):1142-7
Korb DR, Blackie CA

PURPOSE: To determine (1) if the number of meibomian glands yielding liquid secretion (MGYLS) is correlated with dry eye symptoms and (2) the mean number of MGYLS in the nasal, central, and temporal regions of the lower eyelid in a random clinical sample.

METHODS: Subjects presenting for routine eye examinations were recruited (n = 133; 90 females, 43 males; mean age = 50.3 +/- 14.7 years). The sample included symptomatic and asymptomatic individuals using the Standard Patient Evaluation of Eye Dryness questionnaire. Meibomian gland evaluations were performed using a standardized technique and diagnostic instrument.

RESULTS: The mean number of MGYLS in the lower eyelid correlated with dry eye symptoms, p = 0.0002. The mean numbers of MGYLS in each third of the lower eyelid were significantly different, p < or= 0.0001: temporal = 0.27 +/- 0.06, central = 2.14 +/- 0.13, and nasal = 3.10 +/- 0.15. The temporal third of the lower lid was 14 times as likely as the nasal third to have zero MGYLS; 86% of temporal versus 6% of nasal thirds had zero MGYLS.

CONCLUSIONS: This is the first report to document the following: (1) a correlation between the number of MGYLS in the lower eyelid and dry eye symptoms; (2) the number of MGYLS varies significantly across the lower eyelid, with the highest number of MGYLS in the nasal third and the lowest number of MGYLS in the temporal third of the lower eyelid; and (3) instrumentation to standardize diagnostic meibomian gland expression is desirable if not mandatory for the evaluation of meibomian gland function.

Drug news: Resolvyx set to start Phase I/II of RX-10045

Resolvyx announces completion of FDA review period for dry eye drug

Resolvyx Pharmaceuticals has announced that the 30-day review period by the FDA is now complete for an investigational new drug application supporting the use of RX-10045 for the treatment of ophthalmic diseases.

The opening of this investigational new drug (IND) application, submitted in early October 2008, allows Resolvyx to initiate its first clinical trial, which will be a placebo-controlled, Phase I/II study of RX-10045 in 200 patients with moderate-severe dry eye. The company will initiate this study before the end of 2008.

RX-10045 is an isopropyl ester pro-drug of the active Resolvin compound, RX-10008. Resolvyx said that it has conducted in vivo preclinical studies that have demonstrated that RX-10008 is effective in preventing the deleterious effects of dry eye as well as restoring healthy cell function.

In addition, RX-10008 has been shown to be highly effective in preventing clinical signs of dry eye, including decreasing corneal inflammation, reducing corneal epithelial damage and preventing loss of goblet cells (the cells responsible for maintaining tear film integrity).

Abstract: Cepan for demodex??

Thought a few of you would perk up your ears at this. I'd never heard of it, at least that I recall.

[Efficiency and application safety of Cepan cream. Observation of a new indication]
Przegl Lek. 2008;65(5):241-3
Stozkowska W, Raczyńska K

Cepan Cream has been applied in therapeutics for 20 years. This drug is used for topical treatment of burn scars and keloids as well as post-operative scars and contractures. Cepan produces a multidirectional effect. Cepan is well tolerated. Pharmacological property analysis of active ingredients, results of physical, biochemical studies and clinical estimation indicate that the evaluated preparation is both effective and safe. Lately, new information on Cepan effectiveness in eyelids inflammation caused by parasite Demodex folliculorum has been particulary interesting.

Abstract: Azasite vs. Erythromycin ointment

Sounds nice (if uninformative). I don't really know what to make of Azasite for bleph at this point. I've heard all kinds of views from reputable doctors, ranging from considering it a wonderdrug to reserving judgment to dismissing it as pure marketing ploy.

Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis
Ann Ophthalmol (Skokie). 2008 Summer;40(2):68-74
John T, Shah AA.

We tested the efficacy of azithromycin ophthalmic solution for the treatment of chronic mixed anterior blepharitis. The findings suggest that patients with chronic mixed anterior blepharitis can be more effectively treated with azithromycin ophthalmic solution than erythromycin ophthalmic ointment. Patients treated with azithromycin ophthalmic solution show an extraordinary clinical response with shorter treatment duration.

Newsblurb: For the RCE patients out there...

If you think you never see RCE in the press, think again. I've seen two or three of these this year.

Red Wings' Cleary still battling eye injury

DETROIT -- Dan Cleary can't drive, and his depth perception still is a little off.

But he is doing his best to stay in shape while he recovers from an irritation in his left eye.

...Cleary has been bothered for six weeks by the irritation, which originally was caused by a scratched cornea. He scratched the cornea again against the Devils, and still isn't sure how he did it.

His eye was red after practice, and he had trouble keeping it open. He missed his fourth game Monday night, and he will be out at least three more by not traveling with the team.

Cleary said it's not an eye infection.

"I just got another scratch in the eye. I didn't know I had. It just got really bad (last Monday)," Cleary said. "Right now it's turned the corner, and I'm looking at another week. Doctor (Jayne) Weiss has been unbelievable. Without her and Kresgee Eye Institute, I would have been in rough shape."

Cleary said doctors can't heal the scratch and his vision at the same time, which makes his recovery difficult. The scratch will have to heal first, then the vision will improve with steroids and eyedrops.

Abstract: Drug delivery system

For those of you following novel drug delivery systems and 'time-release' type approaches, I thought this was rather interesting. I would guess that a concept like this is dependent on a healthy tear film, which would make it a no-go for delivering dry eye treatments, but who knows.

Mucoadhesive microdiscs engineered for ophthalmic drug delivery: effect of particle geometry and formulation on preocular residence time.
Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4808-15. Epub 2008 Aug 8
Choy YB, Park JH, McCarey BE, Edelhauser HF, Prausnitz MR

PURPOSE: To test the hypothesis that mucoadhesive microdiscs formulated in a rapidly dissolving tablet can increase preocular residence time.

METHODS: Microparticles smaller than 10 mum in diameter were fabricated by emulsification with poly(lactic-co-glycolic acid) as a core material and, in some cases, poly(ethylene glycol) as a mucoadhesion promoter. To examine the effect of particle geometry, microparticles were also cut to have flat surfaces (i.e., microdiscs) and were compared with spherical particles (i.e., microspheres). In vitro mucoadhesion of microparticles was tested on a mucous layer under shear stress, mimicking the human blink. The resultant microparticles were also formulated in two dosage forms, an aqueous suspension and a dry tablet, to test the effect of formulation on the retention capacity of microparticles on the preocular space of rabbits in vivo.

RESULTS: Mucoadhesive microdiscs adhered better to the simulated ocular surface than did other types of microparticles. When a dry tablet embedded with mucoadhesive microdiscs was administered in the cul-de-sac of the rabbit eye in vivo, these microdiscs exhibited longer retention than the other formulations tested in this study. More than 40% and 17% of mucoadhesive microdiscs remained on the preocular surface at 10 minutes and 30 minutes after administration, respectively. Fluorescence images from the eye surface showed that mucoadhesive microdiscs remain for at least 1 hour in the lower fornix.

CONCLUSIONS: This study demonstrated that mucoadhesive microdiscs formulated in a dry tablet can achieve a prolonged residence time on the preocular surface and thus are a promising drug delivery system for ophthalmic applications.

Abstract: Cetuximab and blepharitis

[Blepharitis related to Cetuximab treatment in an advanced colorectal cancer patient.]
Arch Soc Esp Oftalmol. 2008 Nov;83(11):665-8

CASE REPORT: A 52-year-old woman with advanced colorectal cancer was referred to us for treatment of Cetuximab-related ocular side-effects.
Ramírez-Soria MP, España-Gregori E, Aviñó-Martínez J, Pastor-Pascual F

DISCUSSION: Cetuximab is a monoclonal antibody that specifically blocks epidermal growth factor receptor activity. It has recently been approved to treat some tumors such as metastatic colorectal cancer and some ORL cancers. Tolerance to it seems to be better than that to the classic chemotherapeutic agents. However it has several side-effects. Cetuximab-related eyelid toxicity has been recently described, though the pathogenesis has not yet been clearly established (Arch Soc Esp Oftalmol 2008; 83: 665-668).

Survey: Ophthalmologists apparently agree...

...that we need more and better treatments for dry eye, according to a study sponsored by Aton Pharma (the Lacriserts company).

Dry Eye Survey: Ophthalmologists Cite Treatment Limitations/Gaps in Treatment of Moderate to Severe Dry Eye

Nearly all of the ophthalmologists surveyed (94%) believe more treatment
options are needed for moderate to severe dry eye. While 80% feel current
therapies are effective for mild dry eye, only 33% feel they are effective for
moderate dry eye and 67% feel they are only somewhat effective or not very
effective. Only 5% feel current therapies are effective for severe dry eye,
while 56% feel they are somewhat effective and 38%, not very or not at all

Drug/Device news: EGP-437 enrolling for Phase II clinicals

EyeGate Pharma Enrolls First Dry Eye Patient in Phase II Clinical Trial of Lead Product EGP-437
Enrollment Marks Second Clinical Trial Initiation for EGP-437 in 2008

WALTHAM, MA, Nov 10, 2008 (MARKET WIRE via COMTEX) -- EyeGate Pharma, the leader in ocular drug delivery, a specialty pharmaceutical company using iontophoresis technology to safely and non-invasively deliver therapeutics to treat serious ocular diseases, today announced that it has enrolled the first dry eye patient in a Phase II safety and efficacy clinical study of EGP-437 (a combination drug/device). This patient enrollment marks the Company's second clinical trial initiated in the second half of 2008. In July, the Company initiated a landmark Phase II clinical study in severe uveitis, which represented the first U.S. study under an open IND to employ iontophoresis technology to deliver an active compound into the eye.

EyeGate is partnering with Ophthalmic Research Associates (ORA), a leading global clinical research and development organization, located in North Andover, MA. Over the past 30 years, ORA has played a central role in the development and FDA approval of more than 25 ophthalmic products.

"Dry eye is the most prevalent form of ocular discomfort and irritation, and currently has no cure and few treatment options to alleviate symptoms that only provide temporary relief. It is estimated that as many as 20 to 40 million Americans suffer from mild-to-moderate dry eye. Symptoms such as pain, light sensitivity, blurred vision, and irritation decrease the quality of life for patients and can ultimately lead to loss of function and blindness," commented George Ousler, Director of Dry Eye Research at ORA.

The Phase II study is a single-center, randomized, double-masked, placebo-controlled safety and efficacy study of two doses of a corticosteroid solution (EGP-437) over a period of three weeks in dry eye patients. ORA's proprietary Controlled Adverse Environment (CAE) clinical model is being used in this study to support the clinical development of EGP-437.

Drug news: Novel canine dry eye treatment

I thought this was rather interesting:

Vet Develops Implant to Treat Dog Eye Diseases
The biodegradable implant is designed to replace frequent eye drops.

Sinisa Grozdanic, DVM, an assistant professor of veterinary clinical sciences at Iowa State University’s College of Veterinary Medicine, has developed a new treatment method for canine eye diseases. One that is said to be more effective and reliable than using eye drops.

It involves implanting biodegradable medicine into the tissue surrounding a dog’s eye, a process that takes just a few minutes and is done with local anesthetic. The medicine releases gradually and treats the infected eye for about a year.

This is the first time the procedure has been tried to improve auto-immune corneal diseases that can cause pain, redness, inflammation, and other eye problems for canines.

Specifically, Dr. Grozdanic has been looking at how the procedure treats pannus, an inflammation of the corneal surface of the eye and the conjunctiva; keratoconjunctivitis sicca, also known as dry eye; and pigmentary keratitis, an inflammatory condition of the cornea characterized by abnormal pigmentation.

Abstract: Cyclosporine & dry eye

Ho hum....

Ciclosporin use in dry eye disease patients.
Expert Opin Pharmacother. 2008 Dec;9(17):3121-8
Ridder WH 3rd.

BACKGROUND: Dry eye disease is one of the most commonly encountered conditions in eye care, and inflammation is a frequent finding. Ciclosporin has long been used systemically to decrease the deleterious effects of inflammation. Ciclosporin is a calcineurin inhibitor that acts by primarily blocking the action of T cells, decreasing the release of pro-inflammatory cytokines, and preventing the apoptosis of goblet cells.

OBJECTIVE: This article reviews the clinical trials and safety profile of an ophthalmic preparation of ciclosporin in the treatment of dry eye.

RESULTS/CONCLUSION: Clinical trials have demonstrated that ciclosporin minimizes the signs and symptoms of dry eye disease and is not associated with any significant systemic or ocular adverse reaction.

Abstract: Tear film evaporation when wearing contact lenses

Nothing particularly new here....

Contact lens wear affects tear film evaporation.
Eye Contact Lens. 2008 Nov;34(6):326-30
Guillon M, Maissa C.

PURPOSE: The aim of the study was to measure tear film evaporation of both contact lens wearers (CLW) and nonwearers. The hypotheses tested were that (i) amongst CLW tear film evaporation was higher when contact lenses are worn and (ii) tear film evaporation of CLW was higher than nonwearers in the absence of contact lenses.

METHODS: Tear film evaporation rate was measured at 30% and 40% mean humidity. The subjects were divided into 3 groups: (i) CLW wearing contact lenses (n = 111 subjects or 222 eyes), (ii) CLW having not worn contact lenses on the day of the visit (CLW no CL n = 129 subjects or 258 eyes), and (iii) Non-contact lens wearers (NW) (n = 139 subjects or 278 eyes).

RESULTS: The rate of evaporation was similar for the right and left eyes at both humidities. The rate of evaporation was significantly higher for the CLW, than for both CLW no CL and NW. The decrease in the rate of evaporation between the dry (30%) and normal (40%) environmental conditions was significantly lower for the CLW than for the NW. Further, the evaporation rate was significantly greater for the CLW, even after 1 day without contact lens wear, than for the nonwearers.

CONCLUSIONS: The investigation demonstrates that the rate of evaporation is higher in the presence of a contact lens; the effect may be associated with tissue and/or tear film changes as it is, in part, still present 24 hours after contact lens wear. Wearing contact lenses in normal humidity conditions (40%) produces a greater evaporation than that experienced by non-contact lens wearers in low humidity (30%). This could explain the higher prevalence of dry eye complaints among CLW than amongst nonwearers. The study results support the hypothesis of increased evaporation as a contributing factor to contact lens induced dry eyes.

Abstract: Another Systane study

Geez, I've lost count of studies on Systane at this point.

Impact on ocular surface evaporation of an artificial tear solution containing hydroxypropyl guar.
Eye Contact Lens. 2008 Nov;34(6):331-4.
Uchiyama E, Di Pascuale MA, Butovich IA, McCulley JP.

OBJECTIVE: To determine whether any acute effects on evaporative parameters are produced when using a solution containing Hydroxypropyl (HP) (Systane) versus normal saline solution in the eyes of patients with Keratoconjunctivis Sicca at 30 and 60 minutes postinstillation.

METHODS: Randomized double-blinded placebo-control 2-period cross-over clinical trial. Twelve patients with a clinical diagnosis of Keratoconjunctivis Sicca were enrolled in this study. Aqueous tear evaporation was measured at baseline, i.e., before the application of drops on the eye, and at 30 and 60 minutes after instillation of one 40 microL drop of either the HP-Guar containing drop or normal saline on two separate days. Statistical analysis included descriptive data analysis and paired t test.

RESULTS: Hydroxypropyl-Guar resulted in a decrease in aqueous tear evaporation at 30 minutes postinstillation under 25% to 35% relative humidity (RH) (13.2% reduction, P=0.044) and 35% to 45% RH (10% reduction, P=0.028) conditions. The effect of HP-Guar at 60 minutes postinstillation also decreased aqueous tear evaporation but to a lesser degree. Normal saline solution produced no statistically significant increases and decreases of evaporation.

CONCLUSIONS: Aqueous tear evaporation contributes significantly to aqueous tear loss and is humidity dependent. An HP-guar containing solution decreased aqueous tear evaporation 30 and 60 minutes after application. The use of topical medication with known antievaporative effect may be beneficial in dry eye therapy. This effect may also be achieved in normal eyes or sub-clinical dry eyes when in low RH environments.

Abstract: Non-ophthalmologists treating dry eye

Treatment of dry eye disease by the non-ophthalmologist.
Rheum Dis Clin North Am. 2008 Nov;34(4):987-1000, x.
Foulks GN.

Physicians caring for patients who have Sjögren's syndrome often face a particularly difficult task in managing the dry eye that occurs with this disease. The discomfort produced by the condition and the fluctuation of vision attendant to tear film instability are often the most annoying of the clinical symptoms. The understanding of dry eye disease in both its clinical expression and underlying etiopathology has expanded over the past 10 years with implications for management and therapy. The array of potential treatments both topical and systemic has evolved to provide a much more targeted and effective arsenal from which the clinician may choose.

Newsblurb: Boston Sclerals in Houston

News coverage of Boston Scleral satellite in Houston:

Custom-made contact lenses benefit patients with corneal diseases

HOUSTON -- (October 31, 2008) -- Ophthalmologists at Baylor College of Medicine in Houston can now improve impaired vision of patients with damaged or transplanted corneas who cannot wear conventional contact lenses.

"There is a large group of patients who we cannot fit with conventional contact lenses, including trauma patients, patients with irregularly shaped corneas, severe dry eye or bad outcomes from Lasik surgery," said Dr. Stephen Pflugfelder, professor of ophthalmology at BCM and director of the Boston Ocular Surface Prosthesis clinic at the Baylor Eye Clinic. "This remarkable technology allows us to provide a custom-fit, prosthetic, oxygen-permeable contact lens that vaults over the cornea and improves eye sight."

Dr. Anisa Gire, therapeutic optometrist at the Baylor Eye Clinic, will begin fitting patients at the Baylor Eye Clinic at the Medical Building on the McNair Campus of BCM when it opens Nov. 4.

"We are proud to be one of two centers outside of Boston to offer this lens," said Dr. Dan B. Jones, chair and professor of ophthalmology at BCM. "It will be a major resource not only for patients who need the lens, but for the community and area ophthalmologists who previously had to refer patients to Boston to be fitted for the lens."

Abstract: Radiation and lacrimal glands

Identifies a direct relationship between radiation treatment and reduced Schirmer scores.

Lacrimal Gland Radiosensitivity in Uveal Melanoma Patients.
Int J Radiat Oncol Biol Phys. 2008 Oct 27. [Epub ahead of print]
Muller K, Nowak PJ, Naus N, de Pan C, Santen CA, Levendag P, Luyten GP.

PURPOSE: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands.

METHODS AND MATERIALS: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained >/=6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution.

RESULTS: Of the 72 patients, 17 developed a late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES.

CONCLUSION: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES.

Study: Systane and corneal staining

Marketing study straight from the source...

Corneal staining reductions observed after treatment with Systane(R) Lubricant Eye Drops.
Adv Ther. 2008 Nov;25(11):1191-9.
Christensen MT. Alcon Laboratories, Ltd., Fort Worth, Texas

INTRODUCTION: Because of the added emphasis on ocular surface damage included in the Dry Eye Workshop's revised definition of dry eye, an evaluation of corneal staining reductions was conducted for propylene glycol/polyethylene glycol 400-based artificial tear drops (Systane(R) Lubricant Eye Drops; Alcon Laboratories, Fort Worth, TX, USA). METHODS: An analysis was conducted on the percent change from baseline in mean corneal staining scores as reported in two previously published, randomized, double-masked, 6-week clinical studies of Systane. A descriptive comparison was also made between the outcome of the composite analysis and data obtained for Optivetrade mark Lubricant Eye Drops (Allergan, Inc., Irvine, CA, USA). Finally, results were reviewed for an open-label study that investigated corneal staining over a 5-week period after patients discontinued Systane therapy. RESULTS: The composite analysis included 107 Systane-treated patients. The results showed that Systane consistently reduced corneal staining at each visit; the percent change from baseline to day 42 (exit) was 47.1% (P<0.0001). After discontinuing Systane, immediate and significant increases in corneal staining were reported by 20 patients, with an overall increase from baseline to day 35 (exit) of 195.0% (P<0.0001). CONCLUSION: Evaluations of sum corneal ocular staining scores provide clinically meaningful evidence of dry eye severity, and are an important indicator of dry eye disease progression. The results of the composite analysis of two peer-reviewed studies indicate that Systane significantly reduced corneal staining (P<0.0001), indicating a reduction in the severity of dry eye. Finally, discontinuation of Systane results in a rapid increase in corneal staining that further confirms Systane's ability to maintain ocular surface health.

Drug update: Ecabet Sodium

According to a 10/30 press release, results from ISTA's Phase II clinicals on Ecabet Sodium will be released this quarter.

Another resolution


My second resolution is this: I will not get discouraged and quit just because so far I've been an abysmal failure on the first one.

The stack of news reports and studies is getting higher. But the list of move-in tasks and things this house needs doing to it to make it livable is gradually getting a little bit shorter.

The sequel to my original plumbing nightmare set me back a bit, I must admit.

I'm sitting here at the computer (getting ready to blog, believe it or not) when I hear a cataract of water pouring into the furnace room. I rush in and see water pouring out of the pipes and through the floor above. Rush upstairs and find water pouring out of the toilet. Where the blankety blank is the main water cutoff? Panicky call to property manager. She doesn't know, but the neighbor to the north does. Panicky call to Budget Rooter (who know us VERY well by now). Grab Chaidie and run over the field to the neighbor's. Big mean dog chases us off property. That dog knows EXACTLY where the property line is and without body armor I'm not going to argue with him. Run back home. Grab a trash can and haul it downstairs to place at the point where the water is the worst. Upstairs, throw a dozen towels on the bathroom floor to keep the water from escaping to anywhere with carpet. Call property manager again, she can't locate owner. Run out to well house. I don't know what the faucet there does (learned later it was just the pressure tank... I'm still well illiterate) but I twist it all the way to the right. Run back, throw down more towels by bathroom, run down to furnace room, empty the (full) buckets, block the water from escaping to other rooms... Budget Rooter calls to say a guy is on the way, the doorbell rings as soon as they hang up, and the water pressure drops off. Hurray!

The plumber gets it fixed temporarily. Comes back the next day and makes no progress in two hours after snaking the pipes a couple different ways and sending in a camera. Calls in a colleague who has a better camera. They eventually come up with a brillo pad or something like that that they think was stuck in an awkward corner.

If it sounds awful, it's really not. I am so, so, so in love with this place. I ordered a ton of seeds yesterday, and I've been devouring books about sustainable farming. (More about those another time.)

So anyway, I'm sitting here at my desk (downstairs... this is a 2-story house built on a hill) and looking out onto the orchard blanketed in 3" of snow that fell Saturday night. It was 19 degrees at breakfast time this morning... worst arctic blast since 1990 in our temperate climate here. Chaidie is having an absolute ball playing in the snow and you may imagine.

When I think of everything stacked up - haven't even looked at a bill in the last 3-4 weeks we've been so overloaded, and lot of other business matters, not to mention trying to get some curtains on our windows to help keep the heat in and a thousand other little house projects... well it's a little overwhelming, but one foot in front of another, right?

Have a great day and week everyone.