Thursday, June 5, 2008

Abstract: Dry eye at high altitudes....

Jimminy crickets. These people are DRY. More than half of 40+year olds in Tibet are symptomatic and 25% have a Schirmer at or under 5.

Altitude, altitude, altitude. This is why when I get a phone call from an area code in Colorado or New Mexico, I know what I'm going to hear before the conversation starts.

Dry eye syndrome in elderly Tibetans at high altitude: a population-based study in China.
Lu P, Chen X, Liu X, Yu L, Kang Y, Xie Q, Ke L, Wei X.
Cornea. 2008 Jun;27(5):545-51.

PURPOSE: To determine the prevalence of dry eye syndrome, analyze the relationship between dry eye symptoms and signs, and identify associated risk factors for dry eye syndrome in an elderly Tibetan population at high altitude.

METHODS: A population-based survey was conducted from October 2006 to December 2006. A stratified, clustered, random sampling procedure was used to select 2632 native Tibetan people > or = 40 years of age. Symptoms of dry eye were assessed by using a 6-item validated questionnaire. Dry eye syndrome was diagnosed in those subjects having 1 or more symptoms often or all the time. Positive signs included a tear film breakup time of < or = 10 seconds in 1 or both eyes, a Schirmer test score of < or = 5 mm, or a fluorescein score of > or = 1. Correlations between symptoms and signs were analyzed.

RESULTS: Of a total of 2632 eligible subjects, 2229 (84.69%) were examined. The data of 1840 participants were analyzed. Of 1840 participants, 52.4% (95% confidence interval: 50.2-54.7) were symptomatic. The tear film breakup time of < or = 10 seconds was seen in 35.3% (95% confidence interval: 33.1-37.5), a Schirmer test score of < or = 5 mm was seen in 24.7% (95% confidence interval: 22.8-26.7), and a fluorescein score of > or = 1 was seen in 5.8% (95% confidence interval: 4.7-6.9). The correlations between dry eye symptoms and signs were statistically significant. Independent risk factors for dry eye syndrome were positive dry eye signs, increased age, low education level and socioeconomic status, and higher altitude.

CONCLUSIONS: This study shows a high prevalence rate of dry eye syndrome in elderly Tibetans, representing an important health problem.

Abstract: Do your eyes dry out between blinks?

To be honest I'm slightly puzzled as to why we need an "Index" to define this particular baby.

Seems like a sub 1.0 result is the equivalent of a cardiologist saying "Yes, indeed you have heart trouble" which, considering you went to his office complaining of chest pains, you probably already knew.

But hey, if having another number on the chart is helping in some way, fine.

The Ocular Protection Index.
Ousler GW 3rd, Hagberg KW, Schindelar M, Welch D, Abelson MB
Cornea. 2008 Jun;27(5):509-13

The interaction of the time between blinks, or the interblink interval (IBI), and tear film breakup time (TFBUT) helps to regulate the integrity of the ocular surface. A protected surface exists when the TFBUT matches or exceeds the IBI. In contrast, an unprotected surface exists when TFBUT is less than the IBI. This is clinically relevant because repeated intermittent exposure of a tear film-deficient cornea can lead to ocular discomfort and the development of clinical signs, such as keratitis and redness. The relationship between TFBUT and IBI has been quantified by the Ocular Protection Index (OPI), which is calculated by dividing TFBUT by IBI. If the OPI is <1.0, the patient has an exposed ocular surface, putting them at risk for the development of the signs and symptoms of dry eye, whereas if the OPI is >or=1.0, the patient's ocular surface is tear film protected. The OPI has proven to be useful in assessing the factors that may cause or exacerbate dry eye. This review discusses the development and use of the OPI model, its relationship to dry eye, and factors that are known to alter blink rate and tear film integrity.

Newsblurb: Dry eye in the UK

Well gosh. With a title like this...

‘Dry Eye’ syndrome wreaks havoc on Brits

...I thought surely there must be starting to be a major turnaround in public awareness of dry eye in the UK!

Alas, today was not the day - it turned out to be an infomercial for B&L's sodium hyaluronate drop Hycosan. Nevertheless, there has certainly been an increase in the past six months or so in little newspaper blurbs and healthcare Q&A sections covering dry eye... all good signs.

Drug news: Diquafosol in Japan

Per a recent press release by Inspire, partner Santen is expecting to file for approval in Japan later this month.

DURHAM, N.C.--(BUSINESS WIRE)--May 16, 2008--Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today the receipt of a $1.25 million milestone payment from its Asian dry eye partner, Santen Pharmaceutical Co., Ltd., related to the completion of Santen's Phase 3 testing of diquafosol tetrasodium, referred to as DE-089, for the treatment of dry eye. Santen has announced that it expects to file an application by the end of June 2008 for marketing approval in Japan.

Inspire and Santen have a collaborative agreement for the license, development and supply for diquafosol for the therapeutic treatment of ocular surface diseases, including dry eye, in Japan, China, South Korea, the Philippines, Thailand, Vietnam, Taiwan, Singapore, Malaysia and Indonesia. If the product is approved by regulatory authorities, Santen will be responsible for commercialization of the product in the designated countries and Inspire will receive royalties on net sales of the product, based on undisclosed rates specified in the agreement.

Christy L. Shaffer, Ph.D., President and CEO of Inspire, stated, "Santen has been successful in developing and commercializing ophthalmic products in Japan. We are pleased that Santen is moving rapidly toward a Japanese marketing application, which could lead to a meaningful royalty stream for Inspire, if the product is approved."

4/25/08 FDA LASIK hearing: AAO response

The May 2008 message from AAO president David W. Parke II, MD gives some distinct insight to how the AAO feels about what's going on in LASIK-land and to what extent they are interested in initiating any positive changes.

....We need to work harder at screening prospective patients, informing them of their risks and, frankly, managing expectations.

It is indeed gratifying to know that somebody "gets" what complications patients have been telling them for so many years. Though I think they might have dispensed with "managing expectations" as being redundant. If you screen patients carefully, and give them thorough and accurate information about their risks, there are unlikely to be any inappropriate expectations to manage. There might be fewer customers as well, however.

By the by, I am curious to know whether the AAO feels that working harder at "screening" prospective patients includes such things as looking out for contact lens intolerant patients who are probably at higher risk for LASIK dry eye. - Particularly considering Dr. McDonnell, who was representing AAO at the hearing, went out of his way to mention that such patients often seek LASIK, but - so far from cautioning that this may be a warning sign - he also seemed to suggest that LASIK is safer than contacts overall.

Then too, it seems the AAO desire to help LASIK patients retain vital information they may need down the road for cataract surgery:

The Academy is also developing a new “K-card” to be given to patients by their LASIK surgeons, which captures a patient’s preoperative keratometry readings and refraction. It is often difficult to track down this critical data years later, when the patient is in need of cataract surgery or additional eye care. We are exploring ways to store this information digitally for easy retrieval.

I am struggling to suppress some excessively uncharitable thoughts enough to keep my comments within the bounds of civility. But screw it. Some spades just need to be called spades.

The AAO has known about this problem for YEARS. One of its own members, Craig Berger MD (a corneal specialist in Tampa, Florida) has repeatedly tried to persuade them to actually do something about it, going so far as to develop his own internet-based software system (see Safeguard Your Sight) to help patients safeguard the information they will assuredly need eventually - and will almost as assuredly not be able to find when that day comes.

Has the AAO ever showed a particle of interest? Nothing doing. And even now, when the FDA hearing - which resulted in an agreement to add explicit warnings about this problem on the FDA website - has finally goaded them into some semblance of action, will they consider consulting with Dr. Berger after all the time he's invested? Nothing doing. Their idea of helping patients is giving them a card with their vitals.

By golly, that sounds like a wonderful solution which surely all future LASIK patients will appreciate. Lookie! I'm a card-carrying member of the LASIK club! No more glasses. Intead I get to carry a piece of paper in my wallet for the next 30 years which, if I am lucky enough to understand anything about on the day I get it, I will almost certainly forget altogether within the next year.

Funny, this almost reminds me of the card I got from my surgeon in the mail a week after surgery (at which point I couldn't read a stopsign to save my life) stating that I'm legal to drive without corrective lenses. Apparently for a fleeting moment during one of my early post-op exams - probably overcorrected and squinting - I squeezed out a 20/40 OU UCVA in a manifest refraction.

Bottom line: If I was holding out any hopes that the AAO would be just a teensy, weensy bit different from ASCRS in terms of its inclination to promote higher standards than the last 10 years status quo, I am no longer deluding myself.

Abstract: Comparing artificial tears

This is an in vitro comparison of several artificial tears and how long they protect epithelial cells from dessication. As acknowledged in the abstract, whether it happens this way 'in vivo' is up for grabs. Personally I don't find any of it all that interesting because I don't think we should be satisfied with such brief protection in any case.

Americans will not be familiar with these brands... Artelac and Acuolens are hypromellose drops, Vidisic is a carbomer gel, Hyal Drops are sodium hyaluronate, and Viscofresh is carmellose.

Lubricating agents differ in their protection of cultured human epithelial cells against desiccation.
Paulsen K, Maile S, Giebel J, Tost FH
Med Sci Monit. 2008 Jun;14(6):PI12-16

Background: In dry eye, as a disease of the ocular surface, the instillation of artificial tears should compensate for the deficit in wetting and protect the mucosa against drying.

Material/Methods: The desiccation protection of different pharmacological substances was tested using the conjunctival epithelial cell line Chang 1-5c-4 (series 1) and the corneal cell line 2.040 pRSV-T (series 2). On confluent cell growth the cultures were wetted for 20 min with various preservative-free preparations of artificial tears The cell cultures were exposed to a constant air flow for 0, 15, 30 and 45 minutes. Cells were incubated with the vital dye Alamar Blue and subsequently absorption of the oxidised form of the dye was measured using an ELISA-Reader.

Results: Cell survival rates in series 1 after 0, 15, 30, 45 min were (1.02;0.81;0.35;0.32) for Artelac(R) EDO, (0.82;0.69; 0.63;0.54) for Vidisic(R) EDO, (0.77;0.80;0.67;0.70) for Vidisic(R) Fluid EDO, (0.76;0.70;0.36; 0.34) for Acuolens(R), (0.97;0.46;0.35;0.33) for Viscofresh, (0.88;0.85;0.37; 0.33) for Hyal Drops SDU, (0.71;0.44;0.34;0.33) for PBS and in series 2 (1.03;0.84;-0.21;-0.20) for Artelac(R) EDO, (0.89;0.92;0.93;0.86) for Vidisic(R) EDO, (0.96;0.88;0.85;0.85) for Vidisic(R) Fluid EDO, (1.01;0.75;-0.02;-0.03) for Acuolens(R), (0.98;0.17;-0.22;-0.20) for Viscofresh, (0.97;0.83;0.03;-0.21) for Hyal Drops SDU and (0.96;0.26;-0.24;-0.21) for PBS. Vidisic(R) Fluid EDO and Vidisic(R) EDO showed a significantly better protective effect after a drying period of 30 and 45 min.

Conclusions: The protection capability of pharmacological substances against desiccation can be studied in a standardised cell culture system of human epithelial cell lines. Whether these in vitro results are conferrable to the efficacy of artificial tear drops in vivo has to be evaluated in clinical trials.