Friday, October 26, 2007

Study: Benefits of flaxseed oil in Sjogrens/RA/Lupus patients

This looks to have been a decently thorough study (OSDI, Schirmer, BUT, impression cytology) and we sure need studies like this for oral supplements. I particularly like that there was no specific commercial product to be pushed (at least not that can be determined from the abstract).

Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren's syndrome patients

Pinheiro MN Jr et al, Arg Bras Oftalmol 2007 Jul-Aug;70(4):649-55.

PURPOSE: To evaluate if oral flaxseed oil (Linum usitatissimum), which reduces the inflammation in rheumatoid arthritis, may help keratoconjunctivitis sicca's treatment in Sjögren's syndrome patients. METHODS: In a randomized clinical trial, 38 female patients with rheumatoid arthritis or systemic lupus erithematosus associated with keratoconjunctivitis sicca and Sjögren's syndrome were consecutively selected from patients of the Department of Rheumatology of the Amazonas University Hospital. Keratoconjunctivitis sicca diagnosis was based on a dry-eye symptom survey score (Ocular Surface Disease Index - OSDI), Schirmer-I test, fluorescein break-up time, 1% Rose Bengal staining of ocular surface measured by the van Bijsterveld scale. All patients had ocular surface inflammation evaluated and quantified by conjunctival impression cytology, before and after the study. The subjects were divided into three groups with 13 (Group I), 12 (Group II) and 13 (Group III) patients. Group I received flaxseed oil capsules with a final 1 g/day dosis, Group II flaxseed oil capsules with a final 2 g/day dosis and Group III - controls - placebo, for 180 days. RESULTS: Comparing the results at the beginning and at the end of the treatment, statistically significant changes (p<0.05) in symptoms (OSDI), ocular surface inflammation quantified by conjunctival impression cytology, Schirmer-I test and fluorescein break-up time occurred in Groups I e II when compared to controls. CONCLUSIONS: Therapy with oral flaxseed oil capsules 1 or 2 g/day reduces ocular surface inflammation and ameliorates the symptoms of keratoconjunctivitis sicca in Sjögren's syndrome patients. Long-term studies are needed to confirm the role of this therapy for keratoconjunctivitis sicca in Sjögren's syndrome.

Study: Restasis in Sjogrens vs. APLD

Heh. Interesting.

So, dry eye buddies, would you rather have a wetter Schirmer strip or better feeling eyes?

Effect of topical cyclosporine on tear functions in tear-deficient dry eyes.

Jain AK et al, Annals of Ophthalmology 2007 Spring;39(1):19-25

We evaluated the efficacy of topical 2% cyclosporine drops in the treatment of tear-deficient dry eye because of acquired primary lachrymal disease (APLD; 15 patients) and Sjögren syndrome (SS; 15 patients). Symptoms of dryness tended to improve in patients with SS. Schirmer score improved in patients with APLD. Topical CsA 2% drops appears to be safe and effective in the treatment of dry eye patients because in patients with APLD and SS, there is trend toward improvement.

Study: More on immunosuppressants and...

Okay... so what have we here:
1) Something that's supposed to be better than cyclosporine or tacrolimus
2) Another plug for that drug-plug thingymabob.

I'm not sure the "can be highly effective in... dry eye syndrome" bit is simply referencing the known use of cyclosporine in dry eye or whether they're hinting that after ISA-247/LX-211's succesful clinicals for uveitis they're going after the dry eye market (note all these 'wider therapeutic window' comments). Time will tell.

Next-generation calcineurin inhibitors for ophthalmic indications.
Anglade E et al, Expert Opinion on Investigational Drugs, 2007 Oct;16(10):1525-40

Calcineurin inhibitors (CNIs) are potent immunosuppressants that reversibly inhibit T-cell proliferation and prevent the release of pro-inflammatory cytokines by blocking the activity of calcineurin, a ubiquitous enzyme that is found in cell cytoplasm. CNIs can be highly effective in immune-mediated ophthalmic diseases such as uveitis, dry eye syndrome and inflammatory blepharitis, as well as for the prevention of rejection in corneal transplants. ISA-247/LX-211 is a novel CNI that is in Phase III clinical development for the treatment of various forms of non-infectious uveitis. ISA-247/LX-211 is a rationally designed analog of ciclosporin A that exhibits more predictable pharmacokinetic and pharmacodynamic properties and a 4-fold greater calcineurin inhibition than its parent compound, ciclosporin A. ISA-247/LX-211 has been observed to be effective, well-tolerated, and safe in early clinical trials, exhibiting a much wider therapeutic window compared with classic CNIs, such as ciclosporin A and tacrolimus. An alternative approach to widening the therapeutic window for the therapy of ophthalmic disorders lies in local delivery of CNIs through polymeric implants that release the drug over long periods of time. The silicone matrix episcleral implant LX-201 is in Phase III development at present for the prevention of rejection in high-risk cornea transplantation.

Study: Another Smartplug complication

Pyogenic granuloma following Smart Plug insertion.
Arch Soc Esp Oftalmol 2007 Oct;82(10):653-6.

CASE REPORT: We report the case of a 65-year-old woman with dry eye syndrome who was referred because of a red mass in the internal left canthus. Three years previously two Smart Plugs had been introduced into both lacrimal punctums of that eye. We diagnosed a pyogenic granuloma and removed it. Two weeks later a new granuloma developed so both the granuloma and the punctal plug were removed. The patient became asymptomatic following this latter procedure. DISCUSSION: A pyogenic granuloma in a Smart Plug punctum is described. This rare complication is generally associated with the use of silicone punctal plugs, being possibly caused by the chronic irritation of the accumulated detritus and necessitating removal of the plug.

I always get irritated when I read about somebody getting two durable plugs placed in the same punctum. If there's no reliable way to figure out whether the first one is still there, is it ever safe to shove another one in?

Study: Improving contact lens tolerance on dry eyes

Well, I confess I have rather mixed feelings about this one.

On the one hand it's all very sensible and really raises some excellent points. For example, it stresses that choice of contact lens solutions may be just as important as choice of lenses. Reminds me, my sister recently found that Lobob for soft contacts dramatically improved her lens performance.

On the other hand, when read by laypeople I would worry that the details of a study like this get glossed over and instead people take it as encouragement to stubbornly persist in contact lens wear without sufficiently investigating and dealing with the ocular surface problems.

But anyway, I appreciate what appears to be quite a thorough discussion of how to improve contact lens prospects for people with mild dry eye.

Contact lens strategies for the patient with dry eye.
The Ocular Surface, 2007 Oct;5(4):294-307.

ABSTRACT Dry eye is the most common reason for contact lens (CL) discontinuation, and the patient with pre-existing dry eye presents particular challenges to the CL fitter. Poor tear film quality/stability, oxygen deprivation, lens deposits, and adverse reactions to CL solutions all contribute to dry eye, and lid disease, allergies, environmental factors, and medications can further hamper successful CL wear by the patient with dry eye. Health and comfort of the ocular surface is affected by the water content, ionicity, oxygen permeability, and modulus of elasticity of the lens, as well as by surface characteristics, such as protein, lipid, and mucin deposition; protein adsorption; and wettability. The choice of CL cleaning solutions with regard to action, cytotoxicity, and biocompatibility are as important as the choice of the CL itself. With appropriate management of the lid, meibomian gland, and ocular surface conditions that produce dry eye, careful selection of lenses and solutions, and vigilant follow-up, successful CL wear should be achievable for the dry eye patient.

Study: Dry eye, MEGS, and computer users

At last - somebody's actually published something about moisture chambers!!

Even if it is just a plug for a product just about to be commercialized. Even if they did choose a product name that screams GEEEEEK. It's still better than nothing. I've been pushing moisture chambers ever since I acquired my first pair of Panoptx. The benefits can be remarkable and in my opinion there needs to be a concerted effort to dispel the perception that they are a tool only for the end-stage incurable dry eye patient. From the manufacturers, we need products that don't look like the dreaded "dry eye goggles".

So here's the scoop. MEGS (Micro-Environment Glasses). Sigh, this poor product is screaming for marketing help, starting with the name, but never mind that for the moment.

Isolation of the ocular surface to treat dysfunctional tear syndrome associated with computer use.

Yee RW et al, The Ocular Surface 2007 Oct;5(4):308-15.

ABSTRACT Dysfunctional tear syndrome (DTS) associated with computer use is characterized by mild irritation, itching, redness, and intermittent tearing after extended staring. It frequently involves foreign body or sandy sensation, blurring of vision, and fatigue, worsening especially at the end of the day. We undertook a study to determine the effectiveness of periocular isolation using microenvironment glasses (MEGStrade mark) alone and in combination with artificial tears in alleviating the symptoms and signs of dry eye related to computer use. At the same time, we evaluated the relative ability of a battery of clinical tests for dry eye to distinguish dry eyes from normal eyes in heavy computer users. Forty adult subjects who used computers 3 hours or more per day were divided into dry eye sufferers and controls based on their scores on the Ocular Surface Disease Index (OSDI). Baseline scores were recorded and ocular surface assessments were made. On four subsequent visits, the subjects played a computer game for 30 minutes in a controlled environment, during which one of four treatment conditions were applied, in random order, to each subject: 1) no treatment, 2) artificial tears, 3) MEGStrade mark, and 4) artificial tears combined with MEGStrade mark. Immediately after each session, subjects were tested on: a subjective comfort questionnaire, tear breakup time (TBUT), fluorescein staining, lissamine green staining, and conjunctival injection. In this study, a significant correlation was found between cumulative lifetime computer use and ocular surface disorder, as measured by the standardized OSDI index. The experimental and control subjects were significantly different (P < 0.05) in the meibomian gland assessment and TBUT; they were consistently different in fluorescein and lissamine green staining, but with P > 0.05. Isolation of the ocular surface alone produced significant improvements in comfort scores and TBUT and a consistent trend of improvement in fluorescein staining and lissamine green staining. Isolation plus tears produced a significant improvement in lissamine green staining. The subjective comfort inventory and the tbut test were most effective in distinguishing between the treatments used. Computer users with ocular surface complaints should have a detailed ocular surface examination and, if symptomatic, they can be effectively treated with isolation of the ocular surface, artificial tears therapy, and effective environmental manipulations.

New drug news: Alcon / Lantibio and HLA

Once a dry eye drug gets to a certain point in clinicals it's only a matter of time till you hear a big ophthalmic pharma's name connected with it. And considering Alcon's meager dry eye offerings, I'm even less surprised to see that they jumped at the chance to market Lantibio's drug (currently in phase III clinicals) in the US.

Hyaluronic acid drops of various sorts are available as over-the-counter lubricants around the world but not in the US because HLA is not included in the FDA's monograph for ophthalmic demulcents (that little-known and poorly understood way the FDA has of regulating over-the-counter eye lubricants). Probably no one living remembers the last time anyone tried to change that monograph and these days, no one would be motivated to try, because selling drops on a prescription basis is a far more shareholder-friendly idea.

I never actually saw a news release on Alcon's deal with Lantibio and TRB... just saw it buried in their third quarter results announced a few days ago.

New drug news: Re-inspired.

You've got to hand it to them for persistence. Prolacria is not going away, at least not yet.

Inspire tries again with dry eye drug

The News & Observer, Oct 20 2007

Inspire Pharmaceuticals hired a Massachusetts company to test its troubled dry-eye drug, Prolacria.

The medicine has been in regulatory limbo since it failed the second of four clinical trials two years ago.

Prolacria has been tested on 2,000 patients with mixed results. After talks with the Food and Drug Administration, Inspire said in a regulatory filing that it will test the effectiveness of the drug in a particular part of the eye.

Inspire has agreed to pay Ophthalmic Research Associates of North Andover, Mass., up to $34.5 million if the test results get Prolacria regulatory approval.

News & controversy: Patenting damaged rabbits for use in dry eye research?

(Sorry, I'm a couple months late on this one.)

Now I've heard everything. I don't even think I can trust myself to comment on this, so I'll just provide links and quotes.

Can an animal be patented?

Here's a link to the patent application.

Newsblurb: Canine dry eye

Just for a change of pace, I thought I'd post about a veterinary Q&A on canine dry eye that caught my eye. Kind of eye-opening, because doctors are apparently rather more blunt about prognosis and treatments when they're talking about your pooch than about you:

Dog's eye requires lubrication
(Detroit News, Oct 13 2007)

The problem with KCS in younger dogs is that it is more likely to be a case of abnormal or lack of development of the lacrimal gland. Clinical signs may vary considerably between dogs, but typically include ocular discharge, a dull-appearing corneal surface, red eye and failure to open the eye. Corneal changes may include ulceration, vascularization, pigmentation and scarring...
...You will most likely be treating this condition for the rest of the dog's life.

News: Ulster Herald on dry eye

If we think dry eye news coverage is inadequate in the US... well, we're actually doing pretty well compared to many other places. I was very pleased on behalf of our Dry Eye Talk friends in northern Ireland to see this piece:

Not a dry eye in the house

(sigh, every journalist seems to think that is clever)

It's rather, er, barebones, but hey, any coverage is better than no coverage.

Dry eye syndrome is an extremely common condition in which symptoms can range from subtle irritation to inflammation of the tissues of the eyes.

Tears are essential for good eye health since they wash out dust and debris, keep the eye moist and neutralise bacteria that colonise the eye.


In dry eye syndrome, the eye doesn't produce enough tears, or they evaporate off the eye surface too quickly.

The resulting effect can be a gritty, burning or itchy sensation. Occasionally, people complain of excessive watering of the eyes when the tissues try to overcompensate for the lack of moisture.


There are many causes of dry eye syndrome. Many medications, such as antihistamines or oral contraceptives , can cause dry eyes as a side effect, as can general health complaints such as rheumatoid arthritis and rosacea.

Eyes become dry as a natural part of the ageing process, especially during the menopause.

Symptoms can be exacerbated by environments such as central heating, air conditioning , or using the computer for a long period of time.


Dry eyes per se cannot be cured, but the symptoms can be managed. Artificial tears can be used to lubricate the ocular surface, while air humidifiers can add moisture to air that's been heated or conditioned. Silicone plugs can be used to block lacrimal (tear) ducts and retain your natural tears on your eye.

Essential fatty acids can reduce dry eye problems, cold water fish, and flax seed oil may also be beneficial.

If contact lenses are the cause of dry eyes, your contact lens practitioner may switch you to a different lens material.

If you are considering LASIK , dry eyes may disqualify you for the surgery.

New drug news: Civamide in Phase III and acquired by OPKO

Wow, a new one slipped in right under the radar. Well, the more the merrier.

OPKO Health Acquires Rights to Clinical Stage Compound for Dry Eye (October 10, 2007)

The compound, civamide, a proprietary TRPV-1 receptor modulator and neuronal calcium channel blocker, is in Phase III clinical trials in an intranasal formulation to treat various types of pain. Increased tear production was observed in over 50% of the patients receiving civamide, and no systemic side effects were noted. Preliminary evidence suggests that civamide's effects on tear production result from its ability to modify signal transduction pathways present in the human lacrimal gland.

At first blush I kind of wonder how dry eye patients will feel about putting an arthritis treatment up their nose, but then, there's a lot of desperation in the dry eye crowd. If it works, well, I'm sure they'll have a market.

Corporate news: QLT/Forsight Newco acquisition & that new punctal plug technology

This is not directly related to dry eye but this emerging technology about a punctal plug drug delivery system is kind of intriguing (as well as worrying, frankly). Stay tuned on this one.

QLT hits 52-low on eye deal - October 9, 2007

As the first clinical candidate utilizing this cutting edge platform technology, it will target glaucoma, by replacing eye drops, dry eye, allergies and postoperative care. The company expects the products to represent a $6 billion market.

News (not): "New look for LASIK surgery"

I can hardly believe newspapers are still cranking out this kind of thing. Musta been an awfully slow news day in Colorado.

...a 30-year-old outdoor enthusiast in Boulder, long wanted to undergo laser eye surgery so he could ditch the glasses he's worn since the fifth grade.

But it wasn't until recently that laser eye technology became good enough to correct Schaffer's severe astigmatism, a vision problem caused by an irregularly shaped cornea...
During the 10-minute outpatient procedure, Schaffer's surgeon... used a new technology called the IntraLase laser to create a flap in the surface tissue covering each of Schaffer's corneas. Then he used an excimer laser to correct the shape of the corneas, which play a crucial role in reflecting light onto the eyes' retinas.

(Rocky Mountain News, Oct. 2, 2007)

SNORT. New technology? Come on folks. Intralase launched their fourth generation machine in 2006. Femtosecond technology is not new. It's just that it's taken many surgeons till now to amortize their excimers enough to afford one.

But, ahem, forgive my digression from dry eye. Here's what really caught my eye:

Understand the risks: Laser eye surgery provides good results for the vast majority of patients, but complications such as severe dry eye, halos, glare, double vision and vision that worsens at night can occur. The probability of serious long-term complications is less than 0.5 percent.

These sorts of combination statements really bother me because while each individual statement might be defensible or explainable, the overall impression conveyed is false. A normal ignorant consumer would read this and have no way of knowing that "serious long-term complications" does NOT refer to the complications named in the previous sentence - which, according to years of medical studies, clearly have a considerablyl greater than 0.5% rate of occurrence.... My point being that a normal consumer would read this and conclude that they have an 0.5% or less chance of getting severe dry eye.

Sorry, but that's just plain wrong. Read the literature. Heck, read even a standard consent form.

Study: Contamination of ophthalmic solutions (hmm... have we got a solution for you)

Ran across an Ocular Surgery News report on a British Journal of Ophthalmology study (October issue) which found a pretty frightening 8% of eyedrops - particularly steroids, but also including a couple of drops for dry eyes, presumably OTC lubricants - that were in use at a long-term-care facility were contaminated.

One of the comments of the authors:

The frequent contamination during reuse of certain steroid-containing ophthalmic solutions raises the question of whether single-use solutions might be preferred for these and other classes of ocular drugs

Hey, any study that will help encourage development of unpreserved unit doses of any and all prescription eyedrops is welcome around here. Keep it up boys & girls.