Saturday, March 22, 2008

Study: Rats

Probably only of interest to the indefatigable dry eye fans: New rat model for studying dry eye.

Time course of ocular surface and lacrimal gland changes in a new scopolamine-induced dry eye model.
Viau S, Maire MA, Pasquis B, Grégoire S, Fourgeux C, Acar N, Bretillon L, Creuzot-Garcher CP, Joffre C.
Graefes Arch Clin Exp Ophthalmol. 2008 Mar 21

BACKGROUND: The aim of this study was to set up an animal model of dry eye showing disturbance in several components of the lacrimal functional unit, and to describe the time course of the appearance of clinical signs and inflammatory markers.
METHODS: Dry eye was induced in 6-week-old female Lewis rats by a systemic and continuous delivery of scopolamine via osmotic pumps implanted subcutaneously. We first determined the appropriate dose of scopolamine (6, 12.5, or 25 mg/day) for 28 days. In a second set of experiments, we determined markers after 1, 2, 3, 7, 10, 17, or 28 days of a 12.5-mg/day dose. Clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin Muc5AC production were detected on the conjunctival epithelium using immunostaining. The level of IL-1beta, IL-6, TNF-alpha, and IFN-gamma mRNA was evaluated by real-time polymerase chain reaction in conjunctiva and exorbital lacrimal gland (LG). Lipids were extracted from the exorbital LG for fatty acid analysis.
RESULTS: Daily scopolamine doses of 12.5 mg and 25 mg applied for a 28-day period induced keratitis, a decrease in Muc5AC immunostaining density in the conjunctival epithelium, and modifications in the fatty acid composition of the exorbital LG. Animals treated with a 12.5-mg/day dose of scopolamine exhibited an increase in corneal fluorescein staining after 2, 10, and 28 days. All animals exhibited unilateral or bilateral keratitis after 17 days. In the conjunctival epithelium, a significant decrease in Muc5AC immunostaining density was observed at early and late time points, and MHC II expression tended to be increased after 1, 7, 10, and 28 days, without reaching statistical significance. The levels of TNF-alpha, IL-1beta and IL-6 mRNA were increased with scopolamine treatment in both conjunctiva and exorbital LG. Arachidonic acid and the Delta5 desaturase index were significantly increased in the exorbital LG of dry eye animals at each time point.
CONCLUSIONS: This systemic and continuous scopolamine-induced model of dry eye in the rat may represent a helpful tool to investigate moderate dry eye, and makes a contribution in the field of dry eye study.

Friday, March 21, 2008

Study: 5-year study of autologous serum

One of the conclusions of this study is that "Serum eye drops can be effective in treating recalcitrant dry eye syndrome and should be available as a management option when other treatments have failed".

All you MDs out there are listening, I trust, and scrambling through the literature if this is a new concept to you.

Autologous serum in the management of recalcitrant dry eye syndrome.
Lee GA, Chen SX.
Clin Experiment Ophthalmol. 2008 Mar;36(2):119-22

PURPOSE: To evaluate the efficacy and safety of long-term application of autologous serum eye drops treating recalcitrant dry eye syndrome.

METHODS: A retrospective chart review was conducted of patients who had serum eye drops between May 2001 and March 2006. The clinical data collected included sex, age, indications for serum eye drops, frequency of lubricant eye drops use before and after serum eye drop treatment, Schirmer tear function test with anaesthesia, fluorescein staining at baseline and at follow up and changes in subjective symptoms.

RESULTS: There were 46 eyes of 23 patients (19 female and 4 male) in the study group. The average follow-up period was 17.3 months (range 6-55 months). Corneal fluorescein staining of 34 eyes (73.9%) showed improvement at follow up. Sixteen patients (32 eyes, 69.6%) reported a decreased frequency of lubricant use including eight patients (16 eyes, 34.8%) who used only serum eye drops for dry eye treatment. Eighteen patients (35 eyes, 76.1%) reported subjective improvement after using serum eye drops. No significant complications were reported in this study.

CONCLUSION: Serum eye drops can be effective in treating recalcitrant dry eye syndrome and should be available as a management option when other treatments have failed. Meticulous attention must be paid to the possible contamination of the bottle to minimize the risk of infection.

Wednesday, March 19, 2008

Research: Salivating over the prospect of more tears

More news from the Curso Regional Panamericano meeting a week or so ago... According to OSN Supersite, Dr. Horacio Soriano & colleagues have had some pretty remarkable results with salivary gland transplantation.

The researchers found that 100% of patients studied had relief of symptoms, including in the non-operated eye. Only 28% of patients reported requiring lubricating eye drops when outdoors, and all patients had a lower lacrimal pellicle rupture time, except in some cases of Sjögren's syndrome.

Newsblurb: One heckuva brave reporter

New York Times
Lasik Surgery: When the fine print applies to you
Abby Ellin

This is a surprising article... from the remarkably candid firsthand experience with LASIK by a reporter who has dry eye and blurry vision as a result, to the direct quotes from her surgeon, such as "I do see it as a success" and "In 18 years of practice, I’ve never had a patient whose symptoms don’t go away".

BRIEF ASIDE: With all due respect, I really have to wonder how any surgeon could still make this "I've never had a patient who..." type claim - to journalists no less! - when years of published medical evidence about the rates of side effects makes such an assertion simply not credible. The dry eye cat has been out of the bag for far too long to play this tune. In my opinion, if a surgeon in practice for many years claims to have no long-term dry eye patients after lasik, there's only a few possible explanations: 1) The patients with long term dry eye were all "lost to follow-up" i.e. never came back after the 6 month mark. 2) The surgeon has not measured or tabulated the data. 3) The surgeon is, er, "accuracy challenged".

Unsurprisingly, the article has attracted a huge number of comments from readers, ranging from sympathizing fellow dry eye patients to other patients absolutely lambasting the reporter for blaming anyone other than herself (although in the article, she manifestly does blame herself!).

The fact that the NYT ran this article is, in my opinion, one of several recent indications that at long last the LASIK status quo may be changing.

First there were the exciting "new technology" honeymoon news reports in the late 90's leading up to the first FDA approvals of excimer lasers for LASIK, and following cases such as Tiger Woods. Then there was the "Get LASIK" freefall around 2000-2002 when, largely as a result of activism by Ron Link's group The Surgical Eye Foundation, everyone everywhere was reporting on complications. That in turn quickly gave way to a status quo where LASIK was simply a cultural norm and, by and large, journalists had no interest complications. For many years, the only news about refractive surgery seemed to be obligatory slow-news-day technology-update reports or minor business news items.

Is the tide turning? You tell me... Is LASIK going to go out of style?

Research news: Omega 3 and dry eye

Ever since the famous Harvard tuna study there's been quite a number of small projects going on about nutritional supplements and dry eye. Results are starting to creep out though mostly informal and limited-scope studies. No doubt it will be quite awhile before we see enough larger, substantial, well structured studies to get some solid info.

In the meantime I'll report on whatever I see...

According to OSN Supersite, Dr. Fernando de Santiago presented his study results at a recent conference:

PUNTA DEL ESTE, Uruguay — Omega-3 fatty acids help reduce ocular surface inflammation and improve symptoms of dry eye, but they cannot replace standard treatments for lacrimal dysfunction, according to a physician speaking here.

"Omega-3 therapy should be treated as a secondary, not primary, treatment for lacrimal dysfunction," Fernando de Santiago, MD, of Uruguay, said in his presentation at the Curso Regional Panamericano.

In a 4-year study, 20 patients received 1 g of omega-3 per day, and 20 patients received 3 g of omega-3 per day.

"Patients reported feeling better, but it was a subjective assessment since there are no objective methods to show the improvement," he said.

Although high dietary intake of omega-3 essential fatty acids decreases the risk of developing dry eye disease, tear tests done during the study did not find major differences. Therefore, he said, "omega-3 treatment should be used as complementary therapy to tested treatments for light and moderate dry eye, but cannot replace it."


This sort of thing seems to be more packed with questions than answers. What form of Omega 3? I wonder, if the dose had been matched to their weight would it have made a difference to results? (In my current love affair with Barleans cinnamon flavored oil, I'm following their advice about 1T per 100 lbs of body weight.) And on what basis do they state that "Patients reported feeling better"??? That could mean anything from asking "Hey, do you feel bettr now?" (yes/no) to quarterly administration of an OSDI or other scientifically validated questionnaire measuring symptoms.

Tuesday, March 18, 2008

Study: Evening primrose oil and contacts, dry eye

Here's one for all the Omega 3 (or multiple thereof...) supplement enthusiasts. It's a good reminder that we need to be looking at both the details and the big picture of essential fatty acid supplementation. I've heard a lot of people saying things like "But I thought only Omega 3s are good and we have too much Omega 6..." It's definitely not nearly as simple as that.

Oral omega-6 essential fatty acid treatment in contact lens associated dry eye.
Kokke KH, Morris JA, Lawrenson JG.
Cont Lens Anterior Eye. 2008 Feb 27

PURPOSE: Symptoms of dry eye are commonly reported in contact lens wearers and are a frequent cause of non-tolerance. The purpose of the present study is to evaluate the effects of oral treatment with particular omega-6 fatty acids in the form of evening primrose oil (EPO) on subjective symptoms, ocular surface signs and tear film characteristic in patients with contact lens associated dry eye. METHODS: The study design was randomised, double-masked and placebo controlled. 76 female soft contact lens wearers were treated for 6 months with either EPO or placebo (olive oil). Subjects underwent three examinations (baseline, 3 and 6 months). At each examination subjects were given a questionnaire relating to lens comfort and dry eye symptoms and underwent a series of tests of tear film characteristics (tear meniscus height, break-up time), meibomian gland function (lipid layer thickness and quality) and ocular surface parameters (hyperaemia and staining). RESULTS: The EPO group showed a significant improvement in the specific symptom of 'dryness' at 3 and 6 months (p<0.01) and also a significant improvement in overall lens comfort at 6 months (p<0.01). Tear meniscus height was increased in the EPO group at 6 months relative to baseline (p<0.01), although all other objective signs were unchanged. CONCLUSION: This study provides evidence for a beneficial effect of particular orally administered omega-6 fatty acids in alleviating dry eye symptoms and improving overall lens comfort in patients suffering from contact lens associated dry eye.


The timing is pretty amusing. I recently discontinued Evening Primrose Oil (Barleans, of course) from my shop in part of my attempt to tidy up. I've had a few stray bottles I couldn't sell even steeply discounted. If you want them click here.

And by the way, for some very interesting discussions on nutrition, dry eye, and nutritional supplementation, come visit the new(ish) nutrition & dry eye forum at Dry Eye Talk! Dr. Michael Lange has been fielding a wide range of questions and he's been an excellent, much appreciated resource.

Study: Dry eye in Beijing Eye Study

Seems to me a rather remarkable feature of this study is the absence of correlation between symptoms and clinical testing....

And people wonder why it's so hard to get FDA approval for dry eye drugs.

Prevalence of dry eye among adult Chinese in the Beijing Eye Study.
Eye. 2008 Feb 29
Jie Y, Xu L, Wu YY, Jonas JB.

PURPOSE To study the prevalence and associations of dry eye symptoms in adult Chinese.
METHODS The Beijing Eye Study is a population-based study in northern China, which included 4439 of 5324 subjects invited to participate with an age of 40+ years (response rate: 83.4%). For the present study, a random sample was taken consisting of 1957(44.1%) subjects (1112 women; 56.9%). Dry eye symptoms were evaluated with (1) an interviewer-assisted questionnaire; (2) measurement of the tear-film break-up time; (3) assessment of the fluorescein staining of the cornea; (4) slit-lamp-based examination of a meibomian gland dysfunction; and (5) Schirmer's test.
RESULTS Symptoms of a dry eye felt 'often' or 'at all times' were present in 411 subjects (21.0%). In a multivariate analysis, dry eye symptoms were significantly associated with age (P<0.001), female gender (P<0.001; odds ratio (OR): 1.56; 95% confidence intervals (CI): 1.23, 1.98), urban region (P<0.001;OR: 1.89; 95% CI: 1.46, 2.48), low degree of nuclear cataract (P=0.02), and undercorrection of refractive error (P=0.005; OR: 1.42; 95% CI: 1.11, 1.82). All tests for dry eye did not vary significantly between the dry eye group and the normal group.
CONCLUSIONS The dry eye symptoms as evaluated subjectively in a questionnaire occurred in about 21% of the adult population in China, with associations to age, female gender, urban region, and undercorrection of a refractive error. Measurement of the tear-film break-up time, assessment of the corneal fluorescein staining, slit-lamp-based examination of a meibomian gland dysfunction, and Schirmer's test were not significantly associated with dry eye symptoms.

Drug news: Lux Biosciences projects

How fitting... two new births to make up for two recent deaths... Something is apparently in the works from Lux that we'll know more about from ARVO in April.

Lux Biosciences to Provide Update on Four Pipeline Programs, Including Two Phase 3 Clinical Programs, at ARVO


We also will be presenting highly original work with bioerodible polymers as well as a clear, mixed micellar formulation for ocular delivery of our next generation calcineurin inhibitor (LX212 and LX214, respectively). These latter two product candidates are tailor-made for dry eye and other, highly prevalent chronic inflammatory diseases of the eye.”


Further blurb on LX214:

LX214, a novel topical eye drop formulation currently in IND-enabling studies with a target date for entry into the clinic in mid 2008. LX214 is based on Lux’ proprietary next-generation calcineurin inhibitor and is targeted towards other chronic inflammatory diseases of the eye, most notably dry eye syndrome, blepharitis and atopic keratoconjunctivitis.

Drug news: Novartis' Rebamipide and Pimecrolimus are dead

Some dry eye drug projects die long painful deaths and enjoy (er, not quite the word...!) public funerals. Others just slowly stop breathing and no one ever notices.

According to Novartis' 2007 form 20-F, the following are listed as Terminated Projects:

ASM981 (pimecroliums) eye drops for dry eye

OPC759 (rebamipide) eye drops for dry eye

Thank you so much to the reader who brought this one to my attention. I try to scour the quarterly reports from manufacturers but can never manage to keep up with them all.