Friday, August 15, 2008

Abstract: Another Restasis study

YAWN. The usual suspects, the usual results.

In this study, the people who had the mildest dry eye were the most likely to feel better while using Restasis, while the people who had severe dry eye were the most likely to look better to the docs.

Arch Ophthalmol. 2008 Aug;126(8):1046-50.
Evaluation of topical cyclosporine for the treatment of dry eye disease.
Perry HD, Solomon R, Donnenfeld ED, Perry AR, Wittpenn JR, Greenman HE, Savage HE.

OBJECTIVE: To evaluate the use of topical cyclosporine, 0.05% (Restasis; Allergan Inc, Irvine, California), for the treatment of mild, moderate, and severe dry eye disease unresponsive to artificial tears therapy. METHODS: This was a prospective clinical study. One hundred fifty-eight consecutive patients with dry eye disease unresponsive to artificial tears therapy were divided into 3 groups of disease severity: mild, moderate, and severe. Patients were evaluated using the Ocular Surface Disease Index for symptomatic improvement, tear breakup time, fluorescein staining, lissamine green staining, and Schirmer testing. Patients were observed for 3 to 16 months. The main outcome measure was improvement in disease. RESULTS: Forty-six of 62 patients with mild dry eye disease (74.1%), 50 of 69 with moderate disease (72.4%), and 18 of 27 with severe disease (66.7%) showed improvement, with 72.1% improving overall. CONCLUSIONS: Topical cyclosporine shows beneficial effects in all categories of dry eye disease. Symptomatic improvement was greatest in the mild group and the best results in improvement of disease signs were in patients with severe dry eye disease.

Abstract: 60% increase in lacrimal output after acupuncture

Another bunny study rather than humans, but this sure sounds promising! Wish the abstract said when the increase was measured and how long it lasted.

Acupunct Electrother Res. 2007;32(3-4):223-33.
Treatment of intractable dry eyes: tear secretion increase and morphological changes of the lacrimal gland of rabbit after acupuncture.
Gong L, Sun X.

Research on the effect of acupuncture for tear secretion and morphological changes of the lacrimal gland. Acupuncture therapy was given on the rabbits of New Zealand origin. The needles were inserted into the following acupoints around the right eye: Extra 1 (Taiyang), BL 2 ( Zanzhu) and SJ 23 (Sizhukong). The Schirmer Test I (S1T, The Schirmer test is probably the most commonly performed method of measuring aqueous tear production) values pre and post acupuncture therapy were blindly recorded. The lacrimal glands of the normal lacrimal gland group were stained by Hematoxylin and Eosin (HE) for light microscope examination and observed by transmission electron microscope. The S1T value was about sixty percent higher after acupuncture than before. Meanwhile changes also took place in the morphology of lacrimal gland tissu, indicated an active glandular function of synthesis and secretion. Acupuncture can increase lacrimal secretion by stimulating the rabbit lacrimal glandular function of synthesis and secretion.

Abstract: Preocular residence time

All about trying to figure out how to make stuff stay on the eye longer - not just for lubricants, presumably, but for delivery of any ocular drug. They got these "mucoadhesive microdiscs" to stay up to an hour or so.

Mucoadhesive Microdiscs Engineered for Ophthalmic Drug Delivery: Effect of Particle Geometry and Formulation on Preocular Residence Time.Invest Ophthalmol Vis Sci. 2008 Aug 8. [Epub ahead of print]
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 micro-m in diameter, were fabricated by emulsification with poly(lactic-co-glycolic acid) (PLG) as a core material and, in some cases, poly(ethylene glycol) (PEG) as a mucoadhesion promoter. To examine the effect of particle geometry, microparticles were also cut to possess flat surfaces (i.e., microdiscs) and 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 resulting microparticles were also formulated in two dosage forms - an aqueous suspension and 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 the 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 work. More than 40% and 17% of mucoadhesive microdiscs remained on the preocular surface at 10 min and 30 min after administration, respectively. Fluorescence images from the eye surface showed that mucoadhesive microdiscs remain for at least 1 h in the lower fornix.

Conclusion. 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: Inflammatory markers

Inflammatory Markers in the Tears of Patients with Ocular Surface Disease.
Ophthalmic Res. 2008 Aug 7;40(6):315-321. [Epub ahead of print]
Acera A, Rocha G, Vecino E, Lema I, Durán JA.

Purpose: To determine the concentration of interleukins (IL-1beta and -6) and matrix metalloproteinase 9 (pro-MMP-9) in the tears of patients with different ocular surface diseases and to examine the possible relationship between the disorders and molecular inflammation. Methods: 77 patients diagnosed as having different ocular surface disorders and 18 normal control subjects were studied. Patients were routinely examined and separated into 5 groups: (1) control, (2) blepharitis, (3) ocular allergic disease, (4) dry eye and (5) conjunctivochalasis. Ten microliters of tears were collected by a Weck cell sponge. The concentrations of IL-1beta, IL-6 and pro-MMP-9 were measured by enzyme-linked immunosorbent assay, and the MMP-9 activity was evaluated with gelatin zymography. Results: Levels of IL-1beta and IL-6 in tear fluid were significantly higher in conjunctivochalasis (p = 0.0062 and p = 0.0134) than in the control group. Pro-MMP-9 levels were significantly elevated in blepharitis (p = 0.013), in allergic eye disease, in dry eye and in conjunctivochalasis (all p < 0.001), in comparison to controls. Conclusions: Pro-MMP-9 levels in tears are elevated in all of the studied pathologies especially in ocular allergy and conjunctivochalasis. However, IL-1beta and IL-6 were only found to be overexpressed in conjunctivochalasis. These findings illustrate the selective implication of different molecules in each disorder. Copyright © 2008 S. Karger AG, Basel.

Thursday, August 14, 2008

Abstract: Hydrogel vs. silicone hydrogel contacts and dry eye

Hm. Refitting patients with si-hy lenses cut dry eye issues in half. Yup, that's noticeable.

Improving contact-lens related dryness symptoms with silicone hydrogel lenses.
Optom Vis Sci. 2008 Aug;85(8):778-84.
Chalmers R, Long B, Dillehay S, Begley C.

PURPOSE.: To determine dryness symptoms attributable to hydrogel contact lens (HCL) wear by comparing symptoms from age-matched HCL wearers and non-wearers in a cross-sectional study, and to compare that difference to the change in proportion of subjects reporting frequent dryness among HCL wearers after refitting with lotrafilcon A or B silicone hydrogels (SHCLs).

METHODS.: Prevalence of frequent dryness symptoms was compared between HCL and non-wearers from a cross-sectional, historical dataset of Dry Eye/Contact Lens Dry Eye Questionnaires using an age-matched subset of 259 HCL and 246 non-wearers. Prospective change in prevalence of frequent dryness from non-randomized studies (n = 1036), in which daily wear (DW) HCL wearers were refit with lotrafilcon A or B SHCLs, was then compared to the cross-sectional difference between HCL wearers and non-wearers.

RESULTS.: In the Dry Eye/Contact Lens Dry Eye Questionnaires dataset, 47% fewer non-wearers reported frequent dryness than HCL wearers (p = 0.0001). In the lotrafilcon A DW refitting trials, frequent dryness was reported by 67 and 62% fewer subjects for during the day (DD) and end of the day (EOD) dryness (p = 0.0001, both) after refitting. In continuous wear lotrafilcon A trials, there were 63 and 41% reductions in the proportion reporting frequent DD and EOD dryness (p = 0.014 and p = 0.02). Refitting to DW lotrafilcon B yielded a 48 and 46% reduction in the number of subjects reporting frequent DD and EOD dryness (p < 0.0001, both).

CONCLUSIONS.: After refitting DW HCL wearers with either lotrafilcon A or B SHCLs, the proportion of symptomatic wearers was approximately half; an amount similar to the difference in proportion between HCL and non-wearers. This raises the possibility that refitting HCL wearers with SHCLs eliminates the component of dryness that is induced by HCL wear. Further research with more robust experimental design is recommended to test this hypothesis.

Abstract: Contacts and dry eye...

Treatment, Material, Care, and Patient-related Factors in Contact Lens-Related Dry Eye.
Optom Vis Sci. 2008 Aug;85(8):764-72.
Ramamoorthy P, Sinnott LT, Nichols JJ.

PURPOSE.: To examine the effect of general contact lens and material characteristics, care solutions, treatment, and patient-related factors on contact lens-related dry eye.

METHODS.: The data were derived from the Contact Lens and Dry Eye Study, designed as a cross-sectional and nested case-control study including 360 subjects. In separate statistical models, logistic regression was used to examine general contact lens characteristics, specific hydrogel lens materials, care solutions, and patient-related factors associated with dry eye status (controlled for age, gender, and current treatments).

RESULTS.: Several factors were significantly associated with dry eye, including treatment factors such as a recent contact lens refitting (odds ratios [OR] = 5.75, 95% confidence intervals [CI] = 2.14 to 15.46) and use of artificial tears/rewetting drops (OR = 1.09, 95% CI = 1.02 to 1.16), in addition, currently worn materials including Food and Drug Administration (FDA) group II (OR = 2.98, 95% CI = 1.14 to 6.19) and IV (OR = 1.87, 95% CI = 1.08 to 3.24). Significant patient-related factors included decreased overall satisfaction (OR = 3.57, 95% CI = 2.08 to 5.88,), dry eye in the absence of contact lens wear (OR = 6.54, 95% CI = 2.57 to 16.62), reduced daily lens wear duration (OR = 1.16, 95% CI = 1.06 to 1.26), and reduced ability to wear lenses as long as desired (OR = 2.44, 95% CI = 1.30 to 4.54). Care solutions were not associated with contact lens-related dry eye.

CONCLUSIONS.: The strong association of common treatment factors with dry eye status in contact lens wearers suggests that these treatments are not entirely effective. The use of high water content materials was strongly related to dry eye in lens wearers, whereas care solutions were not. Contact lens-related dry eye was also associated with several patient-related factors such as greater ocular discomfort (without lenses), dissatisfaction, and inability to wear lenses for desired durations.

Abstract: ViscoTears, VisLube

Comparing ViscoTears and VisLube (two drops sold in the UK), with just slightly better performance by the latter.

Carbomer and Sodium Hyaluronate Eyedrops for Moderate Dry Eye Treatment.Optom Vis Sci. 2008 Aug;85(8):750-757.
Johnson ME, Murphy PJ, Boulton M.

PURPOSE.: This randomized, double-masked study compared the effectiveness of two commercially available ocular lubricants containing either 0.3% Carbomer 934 or 0.18% sodium hyaluronate (SH) in treating moderate dry eye.

METHODS.: Sixty-five subjects with dry eye were recruited and supplied with eyedrops containing either Carbomer or SH to use for a month. Principle outcome measures were the severity of symptoms of ocular irritation, tear break-up time without (NIBUT) and with (TBUT) fluorescein, and corneal and conjunctival staining with fluorescein and lissamine green, respectively. At the end of the experiment, subjects were also asked, on average, how many times a day they used the treatment and the duration of any postinstillation blur.

RESULTS.: Both Carbomer and SH reduced the symptom severity and ocular surface staining, but neither had a lasting effect on NIBUT or TBUT. The treatment effects of Carbomer and SH were equivalent for symptoms, NIBUT and TBUT. However, for both corneal and conjunctival staining, SH outperformed Carbomer in improving the integrity of the ocular surface. There was no difference in the average instillation frequency of the two products. Visual disturbance after instillation of either formulation was generally short, but lengthy periods of blur were significantly more common after the use of Carbomer.

CONCLUSIONS.: Both of the eyedrops trialled are suitable for patients with moderate dry eye, but of the two, the SH-containing treatment has marginal benefits in therapeutic efficacy and has less propensity to cause visual disturbance.

Abstract: Changes to tear film during sleep


Considering this is focused on what ought to be of keen interest to all of us with serious night dry eye problems, I found this remarkably uninformative. Am I missing something?

Subjective and objective variation of the tear film pre- and post-sleep.
Optom Vis Sci. 2008 Aug;85(8):740-9.
Bitton E, Keech A, Jones L, Simpson T.

PURPOSE.: To date, few studies have correlated the overnight effects of the preocular tear film (POTF) with subjective symptoms. This study investigates the POTF volume and stability, bulbar hyperemia (BH), tear ferning (TF) and the participant's subjective symptoms, pre- and post-sleep.

METHODS.: Thirty subjects were recruited, consisting of two evenly distributed groups who were symptomatic of dry eye (DE) and those that were asymptomatic dry eye, determined using the McMonnies questionnaire. Subjects were evaluated at 10 p.m. (baseline), on waking at 7 a.m., and then hourly until 10 a.m. At each visit, tear meniscus height (TMH), various subjective factors, BH and POTF stability by non-invasive break-up time (NIBUT) were assessed. Tear collection was performed at 10 p.m, 7 and 10 a.m. for TF analysis.

RESULTS.: With the exception of burning, all other symptoms (comfort, dryness, clarity of vision, and grittiness) revealed an overnight change (p < 0.05) within each group, but not between the two groups (p > 0.05). Both the tear meniscus height and BH were elevated upon waking and differed significantly between test times for each group (p < 0.05), but not between groups (p > 0.05). NIBUT was lower for the DE group (p < 0.001). The non-dry eye (NDE) group did not significantly alter over time (p > 0.05), but the DE group did (p = 0.004), with a longer NIBUT in the morning. TF demonstrated a degraded pattern upon waking for both groups (p < 0.05). Most of the changes returned to baseline within an hour after waking.

CONCLUSIONS.: The properties of the POTF undergo a change during extended periods of eye closure and the human POTF is different upon waking to that present immediately before sleep. Most of the parameters determined rapidly revert to baseline levels once the POTF is allowed to refresh.

Abstract: What makes tears stay on the eye

Viscosity ain't the answer. C'mon, folks, Dr. Holly and others figured that out a long time ago. How about somebody go back and read their studies???

Incidental findings: Reading between the ingredient lines in search of possible product names, it sounds to me like Refresh Plus and Soothe were dramatically outperformed by Systane and Refresh Celluvisc (or Liquigel - both are 1% CMC... or could be Theratears liquigel for that matter) in terms of "residence time".

Precorneal residence time of artificial tears measured in dry eye subjects.
Optom Vis Sci. 2008 Aug;85(8):725-31.
Paugh JR, Nguyen AL, Ketelson HA, Christensen MT, Meadows DL

PURPOSE.: The purpose of this investigation was to measure the precorneal residence time of saline and five marketed artificial tears in dry eye subjects using fluorometry.

METHODS.: FITC-dextran, 70 kDa molecular weight, was admixed under sterile conditions (0.1% wt/vol) into buffered saline and the marketed artificial tear formulations of varying viscosity. Precorneal residence time (RT) was measured directly in 16 mild to moderate dry eye subjects, classified by sub-type, in a six-way cross-over, masked and randomized study. FITC-dextran tracer decay with a scanning fluorometer was used to estimate the gross RT (i.e., the time in minutes for the signal to return to baseline).

RESULTS.: All subjects were classified as having non-inflammatory meibomian gland dysfunction except one, who had a mixture of aqueous deficiency and meibomian gland dysfunction. In two separate determinations, the saline RTs were 19.1 +/- 7.4 and 17.6 +/- 8.2 min. The RTs for the formulations varied to some degree by viscosity, with two higher viscosity formulations demonstrating the longest RTs of 36 to 41 min, approximately twice that of saline (p < 0.001 for both 0.4% polyethylene glycol/0.3% propylene glycol, and 1.0% carboxymethylcellulose). An oil emulsion, low viscosity carboxymethylcellulose and moderate viscosity hydroxypropylmethylcellulose-containing formulation were not statistically different from saline (RTs of 18, 22 and 24 min, p values = 0.983, 0.818 and 0.099, respectively).

CONCLUSIONS.: More than two-fold RT differences were found for the higher viscosity, more muco-adhesive formulations compared to saline. However, other formulations provided RTs close to saline, suggesting that RT is influenced by factors other than simple viscosity. Future studies should examine the interplay of spreading characteristics, pseudoplasticity and muco-adhesion relative to RT to determine the individual and cumulative effects on formulation retention.

Abstract: 10-year dry eye trends

Looks like we can glean two pieces of good news from this study:

1. We can drink more coffee.
2. We can drink more booze.

But I'm scratching my head over the reference to vitamins. I do know one or two patients who showed dramatic improvement when they dropped their entire vitamin regimen, though.

Long-term Incidence of Dry Eye in an Older Population.Optom Vis Sci. 2008 Aug;85(8):668-74.
Moss SE, Klein R, Klein BE.

PURPOSE.: To estimate the ten-year incidence of dry eye in an older population and examine its association with various risk factors.

METHODS.: The 43 to 86 year old population of Beaver Dam, WI, was examined in 1988 to 1990 (n = 4926) and 1993 to 1995 (n = 3722). Dry eye data were first collected in 1993 to 1995. Subsequent examinations or interviews occurred in 1998 to 2000 (n = 2827) and 2003 to 2005 (n = 2124). The incidence cohort comprised 2414 subjects not reporting dry eye in 1993 to 1995. Risk factor information, ascertained in 1993 to 1995, included demographics, medical history, cardiovascular disease risk factors, medications, and life-style factors. Ten-year cumulative incidence was estimated by the product-limit method.

RESULTS.: Over the 10-year period, 482 subjects developed a history of dry eye for an incidence of 21.6% (95% confidence interval, 19.9 to 23.3%). Incidence increased significantly (p < 0.001) with age. Incidence was greater in women (25.0%) than men (17.2%, p < 0.001). After adjusting for age, incidence was greater (p < 0.05) in subjects with arthritis, allergy or thyroid disease not treated with hormone, using antihistamines, antianxiety medications, antidepressants, oral steroids or vitamins, and poorer self-rated health. Incidence was less (p < 0.05) in subjects consuming alcohol. It was not significantly associated with blood pressure, hypertension, serum total or high density lipoprotein cholesterol, body mass, diabetes, gout, osteoporosis, cardiovascular disease, smoking, caffeine use, or taking calcium channel blockers or anticholesterol medications. In a multivariable model with time-varying covariates, increased incidence was associated with age, female gender, poorer self-rated health, antidepressant or oral steroid use, and thyroid disease untreated with hormone. It was lower for those using angiotensin-converting enzyme inhibitors or with a sedentary lifestyle.

CONCLUSIONS.: Dry eye incidence is substantial. However, there are few associated risk factors. Some drugs (antihistamines, antianxiety drugs, antidepressants, oral steroids) are associated with greater risk, while angiotensin-converting enzyme inhibitors may be associated with lower risk.

Abstract: Possible breakthrough on Sjogrens diagnostic?

This has potentially important implications for more than dry eye:

By studying the tears of people with Sjogrens Syndrome, people with severe dry eye but not Sjogrens, and people without dry eyes, the study authors found unique characteristics in the tears of people with Sjogrens, and are suggesting that this could lead to a non-invasive way of diagnosing Sjogrens Syndrome.

Tear lipocalin and lysozyme in sjögren and non-sjogren dry eye.
Optom Vis Sci. 2008 Aug;85(8):661-7.
Caffery B, Joyce E, Boone A, Slomovic A, Simpson T, Jones L, Senchyna M.

PURPOSE.: To evaluate the concentration of tear lipocalin, lysozyme, and total protein in Sjogrens Syndrome (SS), non-Sjogrens keratoconjunctivitis sicca (KCS), and non-dry-eyed (NDE) individuals.

METHODS.: Seventy-six subjects were recruited for this study: 25 SS subjects; 25 KCS subjects, and 26 NDE individuals. Symptoms were measured with a visual analogue scale. Tear flow was measured by the Schirmer I test without anesthesia. Tears were collected using an eye wash technique. Total tear protein was quantified using the DC Protein Assay Kit. Tear lipocalin and lysozyme were quantified via Western blotting performed on a Phast System.

RESULTS.: By definition, the SS and KCS groups both had significantly lower mean Schirmer scores (5.12 +/- 5.96 mm and 7.84 +/- 7.35 mm) compared with the NDE group (23.83 +/- 7.85 mm; p < 0.0001). There was no difference in mean Schirmer scores between SS and KCS groups (p = 0.19). The tear film of the SS group was characterized by significantly reduced (p < 0.0001) total protein and lipocalin concentrations compared with both KCS and NDE groups. No difference between the KCS and NDE groups was found in total protein (p = 0.92) or lipocalin (p = 0.19) concentration. In contrast, the concentration of tear film lysozyme was found to be statistically similar in all three groups examined. No statistically significant correlation was found in any group between mean Schirmer values compared with total protein, lipocalin or lysozyme concentration.

CONCLUSION.: Our data demonstrate a biochemical distinction between the Sjogrens group compared with both KCS and control groups, in that both tear lipocalin and total tear protein were significantly reduced. Although correlations were not found between protein measurements and tear flow, a combination of tests including Schirmer I and quantitation of tear film biomarkers may allow for the identification of SS patients without the need for invasive testing.

Abstract: "Designer ophthalmics"

How'd you like somebody to study your tears and come up with a designer drug for you? Sounds awfully appealling, and Dr. Laurie (he's the one behind Lacritin... speaking of which, I need to get an update on that sometime soon) seems to think it's at least conceivable.

Dry Eye and Designer Ophthalmics.
Optom Vis Sci. 2008 Aug;85(8):643-652.
Laurie GW, Olsakovsky LA, Conway BP, McKown RL, Kitagawa K, Nichols JJ.

Expressed sequence tag (EST), proteomic, and antibody capture assays are revealing a level of tear film protein complexity far greater than previously appreciated. A systems biology approach will be needed to fully appreciate function as tear protein doses fluctuate in time through different conditions. Although consensus is growing on what fully constitutes the human tear proteome, questions remain about the source and significance of the approximately 256 tear proteins designated as "intracellular." Many of these may derive from normal cellular turnover and could therefore be informative. A further >183 are designated as "extracellular." Surprisingly, only 4 to 5% of these appear to be dysregulated in the three forms of dry eye preliminarily examined to date. Some differ and a couple overlap, suggesting that disease-specific signatures could be identified. Future dry eye treatment might include recombinant tear protein rescue as a personalized ophthalmic approach to ocular surface disease.

Abstract: Dry eye, corneal sensitivity and cat surgery

Yessss... always pleased to see more research about cataract surgery and dry eye. The results from this one are vaguely reminiscent of some of the LASIK dry eye studies when they used to say we'd all get better within 3 months. Let's hope it's truer of the cat patients.

For those new to this, "phacoemulsification" is a fancy name for the process of sucking the natural lens out of the eye so that an artificial lens can be implanted during a cataract surgery.

Changes in corneal sensitivity and tear physiology after phacoemulsification.

Ophthalmic Physiol Opt. 2008 Mar;28(2):127-34.
Khanal S, Tomlinson A, Esakowitz L, Bhatt P, Jones D, Nabili S, Mukerji S.

PURPOSE: To identify any changes in corneal sensitivity and tear physiology after phacoemulsification and to evaluate the effectiveness of the use of ophthalmic lubricants.

METHODS: The design of the study was longitudinal, parallel, randomised and double masked. Eighteen patients (average age 70.83 +/- 10.66 years, 7 males and 11 females) undergoing phacoemulsification were recruited and divided into three groups of six. In addition to the prednisolone acetate 1% and chloramphenicol 0.5% routinely given to patients postoperatively, the first two groups were given a tear lubricant (Refresh Soothe and Protect, Allergan Inc., Irvine, CA, USA) and saline (Chauvin Pharmaceuticals Ltd, Essex, UK), respectively, and the third was a control group and did not receive any additional eye drops. Tear production, evaporation, lipid layer interferometry and osmolarity along with corneal sensitivity were measured before and 3 days, 2 weeks, 1 month and 3 months after the surgery.

RESULTS: Statistically significant detrimental changes were seen in all parameters of corneal sensitivity and tear physiology immediately after phacoemulsification. Tear physiology recovered within 1 month. Corneal sensitivity did not return to normal levels in 3 months, but a trend towards full recovery was seen. Saline and the tear lubricant were not found to have an effect on the improvement of tear physiology and corneal sensitivity post-surgically.

CONCLUSIONS: Deterioration in corneal sensitivity and tear physiology is seen immediately after phacoemulsification. Corneal sensitivity does not return to preoperative levels until 3 months postoperatively whereas the tear functions recover within 1 month.

Drug News: LX214 update

Lux Biosciences announced on July 31 at ARVO their preclinical results from LX214, a calcineurin inhibitor Lux is "developing as a potential treatment for such conditions as dry eye syndrome, blepharitis, and atopic keratoconjunctivitis."

Click here for full press release

Results announced:
- Concentrations of LX214 (and/or residue) establish therapeutic levels in tear fluid and most ocular tissues, including conjunctiva, cornea, eyelids, sclera and lacrimal gland after single or multiple topical applications of the experimental drug. Blood levels of LX214 remained at or near base line, and there was minimal distribution of LX214 to the opposite, non-treated eye.

- Tissue concentrations of LX214 in the target tissues for ocular immune-mediated diseases were significantly higher than the tissue concentrations of cyclosporine A achieved by twice daily topical application of Restasis® (cyclosporine 0.05%). These results are particularly important given that voclosporin has been shown to be four-fold more potent than cyclosporine A.

- No evidence of clinical irritation was observed in any of the animals treated with LX214.

- No evidence of melanin binding by LX214 was observed.

“These data strongly support the further development of LX214 as a topical product for serious ocular inflammatory conditions as well as for dry eye syndrome,” said Ulrich Grau, Ph.D., President and Chief Executive Officer of Lux Biosciences. “We believe that the product has best-in-class potential based on the preclinical findings.”

Speaking of Lux, check their website for more information on LX214 and LX212. LX212 seems kind of vaguely reminiscent of Lacriserts.

Abstract: An implanted pump for artificial tears

This is what happens when I finally get around to cleaning out my email inbox - I find some medline dry eye alerts that I missed the first time. So I've got a few things coming from July (oops).

Case study of an implanted pump resevoir used to treat a patient in an extreme situation. Interesting concept.

Bilateral infusion pump implants as therapy for refractory corneal ulcers in a patient with CREST syndrome: an interdisciplinary approach.
Arch Ophthalmol. 2008 Jul;126(7):964-7. Links
De Andrés J, García-Delpech S, Pérez VL, Díaz-Llopis M, Udaondo P, Sánchez MT, Salom D

Internal infusion pumps are implantable and programmable systems that have been widely used for years in the management of chronic pain. During the past few years, these devices have had an increasingly prominent role given the possibility of insulin infusions in patients with diabetes mellitus because they provide patients with higher autonomy in the management of their disease, despite the fact that they are expensive systems and require surgery for implantation. These features make internal infusion pumps a suitable therapeutic option for those patients who need to use artificial tears continuously because of severe dry eyes. We report a case of severe eye pain due to xerophthalmia in a patient with CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome who was treated with an implanted pump reservoir.

Abstract: What the diagnostic tests don't tell us

Whoops, missed this one from back in June.

Nothing particularly new here - poor correlation of severity of signs & symptoms of dry eye - but hopefully, the more frequently this gets written up, the more motivation there will be to find some better solutions for the lack of correlation.

Of note however is the "median of 6 tests used in the initial examination" of dry eye patients by the participants in this study. I wonder how many DEZ members had that many tests administered by any of their first five doctors. We as patients need to have higher expectations of our eye doctors and be educated before we walk through that door about the diagnostic procedures that could/should be administered.

Current patterns in the use of diagnostic tests in dry eye evaluation.
Cornea. 2008 Jul;27(6):656-62.
Nichols KK, Baldwin EK.

PURPOSE: To clarify the roles of objective signs and subjective symptoms in the diagnosis and management of dry eye by describing their use by a group of expert practitioners. Dry eye signs and symptoms do not always correlate well, and there is currently some controversy over the ideal roles of signs and symptoms and their actual use in clinical practice. METHODS: A balanced panel of 16 participants in a scientific roundtable on dry eye reviewed 4 patient case studies and completed surveys ranking common diagnostic procedures assessing symptoms and signs by the order in which they would be used. RESULTS: Symptom assessment was the predominant diagnostic method. The objective tests most commonly used during the initial examination were tear breakup time (93%), corneal staining (85%), tear film assessment (76%), conjunctival staining (74%), and the Schirmer test (54%). Most panelists used multiple tests, with a median of 6 tests used in the initial examination. CONCLUSIONS: Subjective symptoms and objective signs are both important in the diagnosis and management of dry eye, with the patient's symptoms and history playing a critical role. Most clinicians use objective signs in dry eye management. However, currently available diagnostic tests do not correlate reliably with symptom severity. Research aimed at developing accurate, objective, responsive measures of dry eye severity is needed.

Monday, August 11, 2008

Abstract: Kids, arthritis and dry eye

Adding to the collection of information on dry eye in kids...

[The dry eye syndrome in children with juvenile idiopatic arthritis][Article in Polish]
Klin Oczna. 2008;110(1-3):35-9.
Lipiec E, Grałek M, Niwald A.
Z Kliniki Okulistyki Dzieciecej Katedry Pediatrii Zabiegowej Uniwersytetu Medycznego w Lodzi.

PURPOSE: The aim of the study was to evaluate the dry eye syndrome in children with juvenile idiopathic arthritis (JIA), and its relation to the immunological markers of the JIA (antynuclear antybodies ANA and rheumatoid factor RF). MATERIAL AND METHODS: The study included 62 children with JIA. The age of patients during the first ophthalmic examination ranged from 9 to 18 years (62 children). A control group consisted of 49 healthy children. The time of observation was 18 months during which the children and adolescents were subjected to complex ophthalmic examinations (including a history of eye discomfort and Schirmer and BUT tests), in the intervals of 9 months. The diagnosis towards dry eye syndrome was made (including a history of eye discomfort and Schirmer and BUT tests). RESULTS: The majority of children with JIA complained of discomfort in the eyes. The difference appeared to be statistically significant between the group of children with JIA and the control group in the range of 5 features. The results of Schirmer test were found to be inadequate in 7 children (13%) and of BUT test in 9 children (15%). In total, inadequate results of Schirmer and/or BUT tests and a high score of discomfort evaluation were detected in 11 patients (17.7%). CONCLUSIONS: 1. The dry eye syndrome may occur in the course of JIA in children without any distinct clinical signs, resulting in subjective symptoms and decreasing the quality of life. 2. No correlation between immunological markers of the JIA and ocular changes was observed.

Abstract: Dry eye and pink eye....

Well, the conclusions on this one say it all: "Patients with dry eye are more likely to have fluoroquinolone-resistant conjunctival bacteria than controls." I thought it was kind of interesting that they did NOT see any difference between patients with plugs and patients without.

Bacteriologic Profile of the Conjunctiva in the Patients with Dry Eye.
Am J Ophthalmol. 2008 Jul 29. [Epub ahead of print]
Hori Y, Maeda N, Sakamoto M, Koh S, Inoue T, Tano Y.

PURPOSE: To assess the conjunctival bacterial profiles in dry eye and their fluoroquinolone susceptibility patterns.

DESIGN: Prospective, observational study.

METHODS: Sixty-seven female patients with dry eye (29 with Sjögren syndrome and 38 without Sjögren syndrome) who received artificial tears were enrolled at Osaka University Hospital in Japan. Twenty-three patients received additional topical steroids. Twenty-six puncta were occluded with plugs. Cultures were obtained with conjunctival swabs at the right eye of the subjects. The minimum inhibitory concentrations of isolated strains were determined for the fluoroquinolones (levofloxacin and gatifloxacin). The profiles of conjunctival bacteria of patients with dry eye were compared with those obtained before surgery from 56 female control patients.

RESULTS: Eighty-eight strains were isolated (48 strains of Propionibacterium acnes, 26 coagulase-negative Staphylococcus [CNS] species, six Staphylococcus aureus strains, and eight others). Of the 26 CNS strains, 17 (65.4%) were fluoroquinolone resistant, including four (33.3%) of 12 methicillin-sensitive CNS and 13 (92.9%) of 14 methicillin-resistant CNS. All methicillin-sensitive S. aureus strains and P. acnes strains were sensitive to fluoroquinolones; one methicillin-resistant S. aureus strain was resistant. There was no significant difference in the conjunctival isolation rates between patients with dry eye and controls. However, the dry eye group had a significantly higher incidence of fluoroquinolone-resistant methicillin-sensitive CNS and of fluoroquinolone-resistant methicillin-resistant CNS than controls (P = .018 and P = .024, respectively). There were no significant differences in bacteria isolated between subgroups with or without punctal plugs and with or without topical steroids.

CONCLUSIONS: Patients with dry eye are more likely to have fluoroquinolone-resistant conjunctival bacteria than controls. These results may help prevent infectious keratoconjunctivitis in patients with dry eye.

Newsblurb: Dry eye seminar

This is old news (a seminar in North Carolina last week) but I happened to see the notice and I'm mentioning it here because I like the idea and I'd like to see more eye doctors hosting events of this kind. You can educate the community about recognizing the symptoms of dry eye and about general tips on caring for mild-to-moderate dry eye, and increase your practice at the same time....

Dry Eye Syndrome seminar
".... Ophthalmology", as a part of their "Vision for Life" series of Patient Education Seminars, will offer a free "lunch and learn" seminar entitled "Dry Eye Syndrome: We're All in the Same Boat, but Where's the Water?" at noon Tuesday in the Hendersonville office location. This talk will be presented by Dr. "...", board certified and fellowship-trained cornea specialist. Lunch will be provided to participants.

Dry eye syndrome is one of the most common eye complaints as we age. It is a result of deficient tear production and may be caused by a number of environmental, genetic or disease processes. Dr. "..." has treated thousands of patients with dry eye syndrome. Come and learn how to recognize the symptoms of this common problem and how to protect your eyes from the effects of dry eye syndrome.

To reserve a place, call "...". Reservations are required and seating is limited.