Wednesday, September 10, 2008

Abstract: New plug insertion technique

Phew! I had no idea that migration during insertion could be that common with punctal plugs! (That basically means a silicone plug that's supposed to sit right at the outside of the puncta where you can see it falls in and moves up the channel.) Seems unlikely if patients are sized correctly?

A New Punctal Plug Insertion Technique to Prevent Intracanalicular Plug Migration.
Am J Ophthalmol. 2008 Sep 3. [Epub ahead of print]
Kaido M, Ishida R, Dogru M, Tsubota K.

PURPOSE: To evaluate the intracanalicular migration rate during plug insertion with a new plug insertion technique compared with a standard technique.

DESIGN: Interventional, nonrandomized, comparative study.

METHOD: Forty-five patients with dry eye syndrome underwent a punctal plug insertion with the new technique, and 33 patients underwent a punctal plug insertion with a standard technique at the dry eye subspecialty outpatient clinic of the Department of Ophthalmology at Keio University. Tear function examinations and ocular surface evaluations, including the Schirmer test, tear film breakup time, fluorescein and Rose Bengal vital staining scores, were performed before punctal plug insertion. Super Flex Punctum Plugs (Eagle Vision, Memphis, Tennessee, USA; Softplug-Oasis Medical Inc, Glendora, California, USA) were implanted in all subjects with both techniques. In total, 120 procedures were carried out with the new technique and 132 procedures with the standard technique.

RESULTS: There were no statistical differences between the two groups in tear function and ocular surface staining scores (P > .05). There was no intracanalicular plug migration with the new insertion technique, whereas there were 18 incidents of intracanalicular migration of 132 standard plug insertion procedures (13.6%).

CONCLUSIONS: The new plug insertion technique seems to be effective in eliminating intracanalicular plug migration during the insertion procedure.

Drug update: Civamide

Just a quickie (not much info): According to a recent interview, Civamide is supposed to enter Phase II clinical trials later this year or early 2009. A press release back in fall of 2007 suggested this was further along, so I had it in the Phase III section of our Clinical Trial Roster but I've now corrected that.

Interview with OPKO Health VP Samuel Reich
Sept 8, 2008

We have a drug called civamide that we are developing. It's a clinical stage drug and we are entering a Phase II trial later this year or early 2009. The clinical stage drug is for dry eye and dry eye is becoming an increasingly big problem and represents a very large market. We see dry eye as an unmet medical need and an important area of focus for OPKO.

Abstract: Ointment in a special case

Ectro-WHAT? My goodness.

As you all know, I officially hate ointments (personally and scientifically) with the exception of Muro 128 for ABMD (though I think Dwelle is a lot more effective). I'm convinced that for the vast majority of dry eye patients there are better options including better lubricants and moisture chambers. But at the end of the day, I'm just a dumb patient. And if they can prove something really does help someone and does not hurt them more than it helps, well and good.

Management of evaporative dry eye in ectrodactyly-ectodermal dysplasia-clefting syndrome.
Optom Vis Sci. 2008 Sep;85(9):E795-801. Links
Ota Y, Matsumoto Y, Dogru M, Goto E, Uchino Y, Endo K, Tsubota K.

PURPOSE: The purpose of this study is to report the features of dry eye and ocular surface disease in an unusual case of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome.

CASE REPORT: A single observational case report of a 22-year-old Japanese male with evaporative dry eye and corneal epithelial disease because of lipid layer abnormality resulting from meibomian gland agenesis was treated successfully with low dose lipid base ointment application.

DISCUSSION: The clinical features of the dry eye and ocular surface disease and management issues are discussed.

CONCLUSION: Low dose lipid base ointment application may be a promising treatment modality for the ocular surface disease in ectrodactyly-ectodermal dysplasia (EEC)-clefting syndrome, which seems to help in alleviating the subjective complaints and in improving the objective clinical findings.

Abstract: Floppy eyelid syndrome

As always I like to see studies highlighting the role of eyelids in dry eye... and I'd also really like to see more information about the successful strategies for combating it without surgery or drugs! I'd really like to see one of you oculoplasts do a little study on Tranquileyes one of these days. Why is it all your patients find out about it from their own research and not from you?
If you're not an oculoplastic surgeon but know someone who is, let 'em know!

Impact of floppy eyelid syndrome in ocular surface and dry eye disease.Optom Vis Sci. 2008 Sep;85(9):814-6.
Mastrota KM.

Floppy eyelid syndrome (FES), a clinically recognized condition of lax and rubbery eyelids, is commonly under-diagnosed. It is associated with chronic papillary conjunctivitis and is often, although not always associated with obesity and obstructive sleep apnea. Symptoms of FES mimic those of ocular surface disease; indeed FES itself can contribute to ocular surface damage. Diagnostic signs of FES can include foreign body sensation, ocular discharge, injection, and eyelid and eyelash ptosis. Palliative topical measures may be inadequate for symptomatic relief necessitating surgical eyelid repair.

Abstract: Eye surface sensitivity in dry eye patients

Unsurprisingly, we have more sensitive corneas and conjunctiva than the general population.

And while I'm sure menopausal 49-year-olds are gratified at being included in the "younger" group, I wonder whether, in light of the well-known role of hormones in dry eye, lowering the threshold for the "older" group might have yielded somewhat different results in the age comparative data.

Conjunctival and corneal hyperesthesia in subjects with dryness symptoms.Optom Vis Sci. 2008 Sep;85(9):867-72.
Situ P, Simpson TL, Jones LW, Fonn D.

PURPOSE: To compare conjunctival and corneal sensitivity in noncontact lens wearing subjects with and without symptoms of ocular dryness, stratified by age and gender.

METHODS: Ninety-seven subjects were enrolled, 54 of whom were asymptomatic and 43 of whom were symptomatic of ocular dryness. A single score for the symptom of dryness was used to classify nondry eye (scores of none to trace) and dry eye symptomatic (scores of mild to severe) groups. The subjects were further stratified into "younger" (19 to 49 years) and "older" age groups (50 to 80 years). Conjunctival and corneal sensitivity of the right eye was measured at the central cornea and temporal conjunctiva, using a computer-controlled pneumatic esthesiometer with stimulus temperature set at 20 degrees C. The ascending method of limits was used to determine the thresholds.

RESULTS: Conjunctival and corneal thresholds were significantly lower in the dry eye symptomatic than in the nondry eye group (both p < 0.01). The conjunctival threshold was lower than the corneal threshold in the dry eye symptomatic group (p < 0.01) but not in the nondry eye group (p > 0.05). Conjunctival threshold in the nondry eye women was lower than the men (p < 0.05). No difference between age groups was found for conjunctival and corneal thresholds in this study (all p > 0.05).

CONCLUSIONS: Conjunctival and corneal sensitivity to pneumatic cool stimulation is increased in subjects with symptoms of ocular dryness. This hyperesthesia seems to be more significant in the conjunctiva.

Abstract: Retention time of drops in the eyes

Much as I suspected: artificial tears, even thick ones, ain't all that much better than saline :) Yes, I know that that wasn't the point of the study.

Retention and retention of effect of topical formulations in dry eye subjects.
Optom Vis Sci. 2008 Sep;85(9):873-9. Links
Paugh JR, Nguyen AL, Huang P, Hwang JS.

PURPOSE: It was the purpose of this investigation to examine both retention time (RT) and retention of effect of two ophthalmic formulations in the same dry eye subjects.

METHODS: This was a randomized, subject-masked cross-over study. Dry eye subjects, characterized by sub-type, were recruited. For direct RT measurement, fluorescein isothiocyanate (FITC)-dextran, 70 kDa molecular weight, was admixed at 0.1% wt/vol concentration into buffered saline (active control) and a viscous marketed artificial tear formulations (test formulation). RT in minutes was estimated directly as the return to baseline intrinsic fluorescence with an objective scanning fluorometer. Retention of effect was measured with a xeroscope as non-invasive breakup time (NIBUT) and by use of a numerical rating scale for comfort.

RESULTS: Eleven subjects, with most being classified as having non-inflammatory meibomian gland dysfunction, completed the study. The RTs averaged 17.7 (+/-10.0) and 26.8 (+/-16.5) minutes for the saline and test formulations, respectively. The averages for NIBUT were 8.73 (+/-6.1) and 19.5 (+/-4.9) minutes, for saline and the test formulations, respectively. Return to baseline for the numerical rating scale comfort averages were 9.91 (+/-4.1) and 20.21 (+/-6.4) minutes for the saline and test formulations, respectively. When residence time was subtracted from the retention of effect measures, no statistical significance was found for the polymeric solution (vs. comfort, p = 0.153; vs. NIBUT, p = 0.109). However, statistical differences were found for direct retention compared against comfort (p = 0.01) and NIBUT (p = 0.004) for buffered saline.

CONCLUSIONS: It seems that these two retention of effect measures are much shorter than RT measured directly. Future work should aim to confirm these findings in additional dry eye sub-types and in those with more severe disease manifestations.

Product reviews in The Dry Eye Shop

Those of you familiar with the Dry Eye Shop know we have extensive Q&A sections on most products (or product categories) as well as a huge helpdesk with a searchable Q&A archive.

However, I never bothered to activate product reviews... partly because there is so much detailed product discussion over on Dry Eye Talk, and partly because of personal bias. I always figure that review sections on internet stores are so heavily edited they might as well be testimonials written by a marketer. And as time went on, it seemed self-defeating to suddenly switch on reviews because if the shop has been around for a long time and there are no reviews, it looks like nobody cared enough to post any.

Today I finally decided to take the plunge and turn on product reviews. I am hoping a lot of our longtime customers will take the time to post their experiences with at least one product they have tried from our shop. It is my hope that this will turn into another major information-sharing resource (in addition to Dry Eye Talk) - a place where people will share not just "I like this" or "I hated that" but specifically what about each product they liked or didn't, how and why certain products helped them, and also share their practical tips & tricks for making the most of each product.

So if you've ever purchased something in The Dry Eye Shop... please, please, do me a huge favor and take a few moments to write about your experience with it. Here's the quickest way:

1. Go to http://www.nexternal.com/tdec

2. Type the product name in the little search box up towards the top right, and click on the product when it comes up.

3. Scroll way down below Customer Questions to the Customer Reviews section and click on "Submit a Review". Please read the directions so as to make the reviews as helpful as possible to others.

Many many thanks in advance to everyone who helps out with this!!

Drug news: SarCode/Sunesis start phase I clinical trials

SARcode and Sunesis Announce Start of Phase 1 Clinical Trial in Ocular Inflammatory Diseases

(Sept 6, 2008)

Just a distant possibility at this point but it's something entering trials that may have a dry eye application later on depending on Phase I results.

SOUTH SAN FRANCISCO, Calif., September 05, 2008 /PRNewswire-FirstCall/ -- SARcode Corporation, a private company focused on small molecule LFA-1 inhibitors to treat inflammatory diseases, and Sunesis Pharmaceuticals, Inc. today announced SARcode's initiation of a Phase 1 clinical trial of a small molecule LFA-1 product candidate for T-cell mediated ophthalmic diseases. Sunesis and SARcode entered into a license agreement providing SARcode with an exclusive license to Sunesis' LFA-1 technology to develop LFA-1 inhibitors in March 2006.

"LFA-1 antagonists mediate both migration and adhesion of the white blood cells to sites of inflammation as part of the body's immune response," said Tom Gadek, Ph.D., chief executive officer of SARcode Corporation. "Lead indications for LFA-1 include dry eye and allergic conjunctivitis, both large indications with unmet medical needs. The results of this study will inform dose selection for several Phase 2 studies to commence in the first half of 2009."

Abstract: Review of role of mucins

Abstract doesn't really tell us anything, but for the mucous-inspired, you might want to track down the full review.

Functions of ocular surface mucins in health and disease.
Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):477-83.
Mantelli F, Arg├╝eso P.

PURPOSE OF REVIEW: The purpose of the present review is to describe new concepts on the role of mucins in the protection of corneal and conjunctival epithelia and to identify alterations of mucins in ocular surface diseases.

RECENT FINDINGS: New evidence indicates that gel-forming and cell surface-associated mucins contribute differently to the protection of the ocular surface against allergens, pathogens, extracellular molecules, abrasive stress, and drying.

SUMMARY: Mucins are high-molecular weight glycoproteins characterized by their extensive O-glycosylation. Major mucins expressed by the ocular surface epithelia include cell surface-associated mucins MUC1, MUC4, MUC16, and the gel-forming mucin MUC5AC. Recent advances using functional assays have allowed the examination of their roles in the protection of corneal and conjunctival epithelia. Alterations in mucin and mucin O-glycan biosynthesis in ocular surface disorders, including allergy, nonautoimmune dry eye, autoimmune dry eye, and infection, are presented.

Abstract: Technique for correcting lid retraction

Some of you who have dry eye from blepharoplasty mishaps might be interested in this one.... The results were impressive in terms of eliminating dry eye symptoms, though there was a significant percentage needing further surgery.

Correction of upper eyelid retraction using deep temporal fascia spacer grafts.
Plast Reconstr Surg. 2008 Sep;122(3):765-74.
Schwarz GS, Spinelli HM.

BACKGROUND: Upper eyelid retraction may occur as a manifestation of infiltrative disease, previous surgery, or trauma. It is associated with dry eye syndrome and corneal compromise. The authors evaluate a lid-lengthening procedure performed through a lid crease incision that uses modified levator recession coupled with autologous deep temporal fascia upper lid spacer grafting.

METHODS: Records of 15 patients (22 lids) treated by a single surgeon were reviewed retrospectively. Dry eye symptoms, scleral show, lagophthalmos, and keratopathy were evaluated. Each patient underwent slit lamp examination and a Schirmer's test.

RESULTS: Degrees of preoperative scleral show and lagophthalmos were 1.6 +/- 0.7 mm and 1.9 +/- 0.7 mm, respectively. Every patient experienced complete resolution of dry eye symptoms, scleral show (p < 0.001), and lagophthalmos (p < 0.001) following repair. Symmetry was achieved in 73 percent of patients. Overcorrection occurred in four lids (18 percent) and required lid-shortening operations in three. There were no instances of undercorrection or recurrence. No major complications were noted. Graft resorption, extrusion, and infection did not occur. Lid margin contour was consistently excellent. Mean follow-up was 30 months.

CONCLUSIONS: The authors' technique is efficacious, durable, and safe. Autogenous deep temporal fascia is easy to harvest and manipulate. Complications associated with other repairs including recurrence and contour irregularities are avoided. Asymmetry, in this series, resulted solely from overcorrection, and the authors' reoperation rate (13.6 percent) compares favorably with that of other methods of repair. Overall patient satisfaction remains excellent. Deep temporal fascia interposition is a powerful technique for the repair of upper lid retraction.