Thursday, December 17, 2009

Dry eye drug clinical trials - roster updated

Phew, what a marathon. I always forget how much work it is to track these drugs down... no wonder I hadn't re-done that page in so long.

I've updated the dry eye drugs clinical trials page on DryEyeZone. There have been far too many changes and additions and subtractions to try to cover in the blog - check them out at the link - but I will just give a quick rundown of the names & status here:

Prolacria, Cyclokat, Rebamipide (I think) and Sirion's ST603 (I think).

COMPLETED PHASE II and headed for Phase III
RX10045, low dose bromfenac,

COMPLETED PHASE II but... no word of any Phase III anytime soon
ecabete sodium, CanFite CF101, EGP437, ALTY0501

Restasis X, Alcon's unknown drug, Perceiva, SAR1118, AL43546, Civamide, lancovutide, (supposedly) androgen tears

PRECLINICAL stuff of interest
ARG101, 102, 103; MIM-D3, Sylentis' ocular pain drug, LX214, LX212, RGN259, lacritin (maybe) and a cyclosporine drug from Zymedis maybe.

Wednesday, December 16, 2009

Abstract: Glaucoma and higher dry eye incidence.

I don't get it. If you had access to all the medication information for these patients, how could you do a study like this and NOT report the percentages using glaucoma meds preserved with BAK - since we already pretty much know that's the link between glaucoma patients and dry eye?

Characteristics of respondents with glaucoma and dry eye in a national panel survey.
Clin Ophthalmol. 2009;3:645-50. Epub 2009 Nov 16.
Schmier JK, Covert DW.
Exponent Inc., Alexandria, VA, USA;

BACKGROUND: There is an increasing body of evidence strongly suggesting that glaucoma medications may contribute to ocular surface disease and development of dry eye.

OBJECTIVE: To identify glaucoma patients with dry eye, using a nationally representative sample, and to compare clinical and treatment characteristics with controls without dry eye.

METHODS: Patients taking intraocular pressure-lowering medications were identified from the Medical Expenditure Panel Survey. A matched cohort without glaucoma served as controls. Dry eye was identified by diagnosis or use of prescription or over-the-counter medications. Demographic and clinical characteristics and medication use patterns were compared.

RESULTS: The analysis identified 629 respondents with glaucoma and 6,934 controls without glaucoma. Dry eye was more common among glaucoma respondents than nonglaucoma controls (16.5% vs 5.6%, P < 0.0001). There was a nonsignificant trend for respondents with dry eye to report higher rates of glaucoma adjunctive therapy use compared to those without dry eye (44.2% vs 35.0%, P < 0.076). Prostaglandin analogs were the most common glaucoma medication.

CONCLUSIONS: This analysis found that the rate of dry eye was higher in patients with glaucoma than in controls. The use of glaucoma adjunctive therapies may increase the rate of dry eye in glaucoma patients.

Abstract: IBS and dry eye

Ocular manifestations in a community-based cohort of patients with inflammatory bowel disease.
Inflamm Bowel Dis. 2009 Dec 8. [Epub ahead of print]
Cury DB, Moss AC.
Center of Bowel Inflammatory diseases, Clinica Scope, Campo Grande-MS, Brazil.

BACKGROUND:: Ophthalmologic diseases in patients with inflammatory bowel disease (IBD) have been reported with varying frequency, mostly from tertiary referral centers. The aim was to describe the spectrum of ophthalmologic conditions in patients with IBD in a community setting and to compare it with a control non-IBD cohort.

METHODS:: A prospective cohort of patients with Crohn's disease (CD), ulcerative colitis (UC), and non-IBD controls underwent evaluation by an ophthalmologist, including visual acuity, slit-lamp exam, and assessment of lacrimal output.

RESULTS:: The ophthalmologic exam was completed in 112 subjects; 48 with CD, 40 with UC, and 24 controls. Active intestinal disease was present in 52/88 (59%) of the IBD patients, and 79/88 (89%) were taking 5-aminosalicylates (5-ASAs). The IBD and control populations had similar age and gender profiles. Patients with IBD were more likely to report ocular symptoms (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.5-20), particularly dry eyes (OR 5.3, 95% CI 1.4-19), than the control population. On objective exam, 42% of IBD patients had evidence of dry eyes. In a univariate analysis, 5-ASA use was associated with an increased risk of ocular symptoms (OR 7.4, 95% CI 0.9-64), and 5-ASA use >3 g per day was associated with an increased odds ratio of dry eyes (OR 15, 95% CI 1.9-122). Active disease was not associated with eye symptoms or dry eyes. Other eye conditions such as episcleritis, uveitis, or cataracts were infrequent in this cohort.

CONCLUSIONS:: Patients with IBD in the community frequently have dry eyes. This is associated with 5-ASA use, particularly doses >3 g per day. Whether this is a surrogate marker of disease severity is unclear. Inflamm Bowel Dis 2010.

Device news: TearLab approved in Canada

TearLab Achieves Health Canada Approval
December 8, 2009 - CNN Money

SAN DIEGO, Dec. 8, 2009 (GLOBE NEWSWIRE) -- OccuLogix, Inc. dba TearLab Corporation (Nasdaq:TEAR) (TSX:TLB), announced today that Health Canada has issued a Medical Device License for the TearLab Osmolarity System. TearLab is intended to measure the osmolarity of human tears to aid in the diagnosis of patients with signs or symptoms of Dry Eye Disease (DED), in conjunction with other methods of clinical evaluation. The Health Canada license allows the company to immediately begin marketing the system in Canada.

"TearLab represents an excellent solution for practitioners and patients alike, as it offers a rapid and very easy to undertake screening for tear osmolality values in the practice, with no discomfort to the patient," stated optometrist and researcher, Lyndon Jones PhD. Dr. Jones is a professor at the University of Waterloo's School of Optometry and Associate Director of the Centre for Contact Lens Research and has used the TearLab device in a variety of studies for several months.

Elias Vamvakas, Chairman and Chief Executive Officer of TearLab Corporation said, "This Health Canada approval is another significant regulatory and commercialization milestone for our Company. In many respects, Canadian optometrists and ophthalmologists have been at the forefront of eye care innovation. Accordingly, we are confident that they will quickly adopt TearLab as an adjunct to their practices."

Abstract: IntraLase, flap position & dry eye


So where was the OSDI at 12 months? Any interesting outliers? Define "mild". How about the bottom line: Were there any patients in serious pain a year later?

I thought the flap position thing was put to bed in the last several dozen studies. Don't we have more interesting things to study about dry eye and LASIK than proving or disproving whether flap position matters? Or demonstrating yet again, to the consternation of all those in our online communities who had femtosecond laser flaps, that persistent dry eye Does Not Happen, and therefore presumably Did Not Happen to them?

Dry eyes and corneal sensation after laser in situ keratomileusis with femtosecond laser flap creation Effect of hinge position, hinge angle, and flap thickness.
J Cataract Refract Surg. 2009 Dec;35(12):2092-8.
Mian SI, Li AY, Dutta S, Musch DC, Shtein RM.
Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.

PURPOSE: To determine whether corneal sensation and dry-eye signs and symptoms after myopic laser in situ keratomileusis (LASIK) surgery with a femtosecond laser are affected by varying hinge position, hinge angle, or flap thickness. SETTING: University-based academic practice, Ann Arbor, Michigan, USA.

METHODS: This prospective randomized contralateral-eye study evaluated eyes after bilateral myopic LASIK with a femtosecond laser (IntraLase). Superior and temporal hinge positions, 45-degree and 90-degree hinge angles, and 100 microm and 130 microm corneal flap thicknesses were compared. Postoperative follow-up at 1 week and 1, 3, 6, and 12 months included central Cochet-Bonnet esthesiometry, the Ocular Surface Disease Index questionnaire, a Schirmer test with anesthesia, tear breakup time (TBUT), corneal fluorescein staining, and conjunctival lissamine green staining.

RESULTS: The study evaluated 190 consecutive eyes (95 patients). Corneal sensation was reduced at all postoperative visits, with improvement over 12 months (P<.001). There was no difference in corneal sensation between the different hinge positions, angles, or flap thicknesses at any time point. The overall ocular surface disease index score was increased at 1 week, 1 month, and 3 months (P<.0001, P<.0001, and P = .046, respectively). The percentage of patients with a TBUT longer than 10 seconds was significantly lower at 1 week and 1 month (P<.0001).

CONCLUSIONS: Dry-eye syndrome after myopic LASIK with a femtosecond laser was mild and improved after 3 months. Corneal flap hinge position, hinge angle, and thickness had no effect on corneal sensation or dry-eye syndrome.

Abstract: Lipid mediators in corneal injury & repair

Significance of lipid mediators in corneal injury and repair.
J Lipid Res. 2009 Nov 3. [Epub ahead of print]
Kenchgowda S, Bazan HE.
Louisiana State University Health Sciences Center, United States.

Corneal injury induces an inflammatory reaction and damages the sensory nerves that exert trophic influences in the corneal epithelium. Alterations in normal healing disrupt the integrity and function of the tissue with undesirable consequences, ranging from dry eye and loss of transparency to ulceration and perforation. Lipids play important roles in this complex process. While lipid mediators such as platelet activating factor (PAF) and cyclooxygenease-2 (COX-2) metabolites contribute to tissue damage and neovascularization, other mediators, such as the lipoxygenase (LOX) derivatives from arachidonic acid (AA), 12- and 15-hydroxy/hydroperoxyeicosatetraenoic acids (12- and 15-HETE) and lipoxin A4 (LxA4), act as second messengers for epidermal growth factor (EGF) to promote proliferation and repair. Stimulation of the cornea with pigment epithelial derived factor (PEDF) in the presence of docosahexaenoic acid (DHA) gives rise to the synthesis of neuroprotectin D1 (NPD1), a derivative of LOX activity, and increases regeneration of corneal nerves. More knowledge about the role that lipids play in corneal wound healing can provide insight into the development of new therapeutic approaches for treating corneal injuries. PAF antagonists, lipoxins and neuroprotectins can be effective therapeutic tools for maintaining the integrity of the cornea.

Abstract: Castor oil drops

Interesting. But what is this "significant decrease in ocular symptoms" in the conclusion since nothing was mentioned in the methods about assessing symptoms? Methods, methods, methods people, pleeeez. We need consistent ways to compare these things. OSDI may not be perfect, but it's what we've got till someone comes up with something better.

Effect of castor oil emulsion eyedrops on tear film composition and stability.
Cont Lens Anterior Eye. 2009 Dec 4. [Epub ahead of print]
Maïssa C, Guillon M, Simmons P, Vehige J.

OTG Research & Consultancy, London, UK.

PURPOSE: An emulsion eyedrop containing castor oil has been shown to modify the tear film lipid layer and increase tear film stability. The primary objectives of this investigation were to measure the prevalence of castor oil in the tear fluid over time and quantify the effects on the lipid layer. A secondary objective was to quantify the initial effects on ocular symptomatology.

METHODS: The investigation was an open label pilot study on 5 normal and 10 dry eye subjects. A single eyedrop (Castor oil emulsion, Allergan) was instilled in each eye; the tear film appearance and composition were monitored for 4h via in vivo visualisation using the Tearscope and post in vivo tear samples analysis by HPLC.

RESULTS: Combined results for both normal and dry eye subjects showed that castor oil was detected up to 4h after a single eyedrop instillation and associated with an increase in the level of tear film lipid. The relative amount of various lipid families was also changed. An increase in tear lipid layer thickness was significant up to one hour post-instillation for the symptomatic sub-population. The changes in tear film characteristics were associated with significantly lower symptoms up to four hours post-instillation for the symptomatic sub-population.

CONCLUSION: This pilot investigation showed that castor oil eyedrops achieved a residence time of at least four hours post-instillation, producing a more stable tear film and an associated significant decrease in ocular symptoms over the entire follow-up period for the symptomatic subjects.

Abstract: Corneal sensitivity & Restasis

I know it seems counterintuitive to dry eye patients whose pain sensations are so heightened that at the same time, people with dry eyes actually have a decrease in corneal sensitivity. Anyway, this study looks at improvement (increase) in corneal sensitivity with Restasis treatment.

Corneal and Conjunctival Sensitivity in Patients With Dry Eye: The Effect of Topical Cyclosporine Therapy.
Cornea. 2009 Dec 3. [Epub ahead of print]
Toker E, Asfuroğlu E.
From the Department of Ophthalmology, Marmara University Medical School, Istanbul, Turkey.

PURPOSE:: To evaluate changes in mechanical sensitivity of cornea and conjunctiva in patients with dry eye disease unresponsive to artificial tears therapy and to investigate the effect of topical cyclosporine therapy on sensitivity of the ocular surface.

METHODS:: Thirty-seven patients with dry eye disease and 35 healthy control subjects were enrolled to this prospective study. All patients included in the study completed a 3-month run-in period of using nonpreserved artificial tear supplements, but all failed to achieve adequate subjective or objective improvement. Patients were then instructed to use topical cyclosporine A 0.05% twice a day. Pre- and posttreatment (1, 3, and 6 months) evaluations included, corneal and conjunctival sensitivity testing with the Cochet-Bonnet esthesiometer, subjective symptom scoring, fluorescein and lissamine green staining, Schirmer test, and tear breakup time (BUT).

RESULTS:: Conjunctival and corneal sensitivities were significantly lower in patients with dry eye compared with controls (P < 0.0001). In patients with dry eye, corneal sensitivity correlated positively with conjunctival sensitivity and negatively with ocular surface staining scores. Conjunctival sensitivity correlated negatively with the duration of dry eye disease, the total symptom severity score, and the severity of dryness symptom and positively with Schirmer test and tear BUT. Corneal and conjunctival sensitivities did not change significantly after artificial tear therapy (P > 0.05). After topical cyclosporine, statistically significant improvements from baseline were observed in corneal sensitivity at 3- and 6-month visits (P < 0.001). For conjunctival sensitivity, statistically significant improvements from baseline were seen at all follow-up visits (P < 0.0001). Topical cyclosporine treatment also led to significant improvements in symptom scores, Schirmer test, tear BUT, and ocular surface staining scores (P < 0.0001).

CONCLUSIONS:: The mechanical sensitivity of cornea and conjunctiva to tactile stimulus is reduced in patients with dry eye. Our findings suggest that topical cyclosporine may be effective in improving this reduced mechanical sensitivity of the ocular surface.

Abstract: Temporary plug complication

It might sound like an ambiguous modifier but it's actually even more of a misnomer, because neither the plug nor the complication were particularly short-lived. The plug was supposed to be temporary, only, three years later it still wasn't, and things got a little complicated.

Ophthal Plast Reconstr Surg. 2009 Sep-Oct;25(5):413-4.
Canaliculitis with a papilloma-like mass caused by a temporary punctal plug.
Ahn HB, Seo JW, Roh MS, Jeong WJ, Park WC, Rho SH.
Department of Ophthalmology, College of Medicine, Dong-A University, Busan, Korea.

Absorbable plugs are used before attempting permanent occlusion to observe whether the patient will be amenable to treatment for dry eye. Little is known about the complications of absorbable plugs. The authors present a case of canaliculitis with a papilloma-like mass caused by long-standing unabsorbed collagen plug that had been placed 3 years earlier. This is an uncommon clinical presentation that may be encountered in patients who have canaliculitis symptoms and a history of intracanalicular temporary plug placement.

Abstract: Seborrheic dermatitis bleph treated with fluconazole

Treatment of malassezia species associated seborrheic blepharitis with fluconazole.
Folia Med (Plovdiv). 2009 Jul-Sep;51(3):57-9.
Zisova LG.
Department of Dermatological and Venereal Diseases, Medical University, Plovdiv, Bulgaria.

The AIM of the present study was to evaluate the therapeutic effect of fluconazole (FungoIon) in patients with seborrheic blepharitis.

PATIENTS AND METHODS: Four seborrheic blepharitis patients with Malassezia spp. positive cultures on Dixon's agar were treated with fluconazole (Fungolon) (0.200) weekly for 4 weeks.

RESULTS: The therapeutic effect of the treatment was positive in all patients--the clinical symptoms withdrew and cultures became mycologically negative.

CONCLUSION: The results indicate that antifungal agents are efficient in the treatment of seborrheic dermatitis.

Abstract: Seborrhoeic dermatitis and dry eye

Acta Ophthalmol. 2009 Nov 24. [Epub ahead of print]
Impression cytology and ocular surface characteristics in patients with seborrhoeic dermatitis.
Karalezli A, Borazan M, Dursun R, Kiyici H, Kucukerdonmez C, Akova YA.
Department of Ophthalmology, Baskent University School of Medicine, Ankara, Turkey.

Purpose: To evaluate the clinical findings, tear film functions and ocular surface changes in patients with seborrhoeic dermatitis.

Methods: This prospective study involved 63 patients with seborrhoeic dermatitis (Group 1) and 65 control subjects (Group 2). Best-corrected visual acuity measurement, slit-lamp examination, Schirmer I test, tear film break-up time (BUT), Rose Bengal staining and conjunctival impression cytology were performed in all patients. Subjective ocular complaints were scored using an Ocular Surface Disease Index (OSDI) questionnaire. Results between the two groups were compared.

Results: In group 1, meibomitis, blepharitis and conjunctival hyperemia were seen significantly more frequently than in group 2 (p < 0.001). Impression cytology revealed grade 0 changes in 25 (39.6%) eyes, grade 1 changes in 22 (34.9%) eyes, grade 2 changes in 13 (20.6%) eyes and grade 3 changes in 3 (4.7%) eyes in group 1, whereas grade 0 changes in 48 (73.8%) eyes, grade 1 changes in 11 (16.9%) eyes and grade 2 changes in 6 (9.2%) eyes were seen in group 2 (p = 0.032). Mean goblet cell density was 795 +/- 55 cells/mm(2) in group 1 and 1820 +/- 100 cells/mm(2) in group 2 (p < 0.001). Mean Schirmer I and mean BUT results were statistically lower in group 1 than in group 2 (p = 0.043 and p < 0.001, respectively). Mean Rose Bengal scores and mean OSDI scores were statistically higher in group 1 than in group 2 (p = 0.002 and p < 0.001, respectively).

Conclusions: Our data show that patient with seborrhoeic dermatitis has decreased tear production, tear film instability and significant degeneration of the ocular surface epithelium, compared with normal subjects.

Abstract: In vivo confocal microscopy of Sjogrens goblet cells

In vivo confocal microscopy of conjunctival goblet cells in patients with Sjogren syndrome dry eye.
Br J Ophthalmol. 2009 Dec 2. [Epub ahead of print]
Hong J, Zhu W, Zhuang H, Xu J, Sun X, Le Q, Li G, Wang Y.
Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, China.

BACKGROUND: To study the morphology and the density of conjunctival goblet cells (GCs) in patients with Sjögren's syndrome dry eye with in vivo laser scanning confocal microscopy (LSCM), and to explore its correlation with the goblet cells (GCs) density detected by impression cytology in vitro.

METHODS: A total of 43 Sjögren's syndrome dry eye patients were recruited. All were required to fill in the Ocular Surface Disease Index Questionnaires. The tear break-up time was measured, followed by corneal fluorescein staining examination and Schirmer I test. The images of conjunctiva were taken by the Heidelberg retina tomography (HRT-II)/Rostock cornea module. Finally, the specimens for impression cytology were obtained. SPSS 13.0 software was used to analyze the data.

RESULTS: Tear film function test showed that all patients had moderate to severe dry eye. The goblet cell in LSCM images was characterized as a large hyperreflective oval-shape cell with relatively homogeneous brightness. Though GCs density assessed by LSCM (332 +/- 137) cells/mm(2) was higher than that measured by impression cytology (200 +/- 141) cells/mm(2), they showed a significant positive correlation, rho=0.908 (p<0.05).

CONCLUSION: Conjuctival GCs could be easily discriminated under the LSCM. LSCM may be a valuable tool in monitoring the progress and the follow-up of patients with Sjögren's syndrome dry eye.

Abstract: Dry eye epidemiology... in Shanghai

Dramatically different results here versus the corresponding study in Jeddah. These ones look substantially more believable.

[Epidemiologic study of dry eye in populations equal or over 20 years old in Jiangning District of Shanghai]
[Article in Chinese]
Zhonghua Yan Ke Za Zhi. 2009 Jun;45(6):486-91.
Tian YJ, Liu Y, Zou HD, Jiang YJ, Liang XQ, Sheng MJ, Li B, Xu X.
Department of Ophthalmology, First People' s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, China.

OBJECTIVE: To investigate the prevalence of dry eye in populations equal or over 20 years old in Jiangning District, Shanghai, China.

METHODS: This was a cross-sectional study. From September 2008 to January 2009, 6 small districts including 21,102 people of Jiangning District were randomly selected as survey venues by Department of Ophthalmology in First People's Hospital affiliated to Shanghai Jiaotong University. Then, 1266 people as the selected residents were enrolled, which was figured out through the random cluster sampling procedure. Every participant completed dry eye questionnaire, the ocular surface disease index (OSDI), and a series of examination including slit-lamp microscope, tear-film break-up time (BUT) , Schirmer I test, and fluorescein staining of the cornea (F1). The diagnosis of dry eye was referred to the well-accepted domestic diagnostic criteria The SPSS11. 0 software was used to analyze the database, t . test, chi2 test, one-way-ANOVA and Logistic regression were used for analysis.

RESULTS: One thousand and eighty five residents finally took part in this study, and the inclusion ratio was 85.70%. Three hundred and twenty six individuals, including 101 men and 225 women, were diagnosed as dry eye, and the prevalence rate was 30.05%. The prevalence of dry eye in the female (33.78%) was higher than that of the male (24.11%) (chi2 = 11.46, P < 0.01). The prevalence of dry eye in people over 50 years old was higher than that under 50 years (chi2 = 94.50, P < 0.01). The figure of Schirmer I test and BUT decreased in elder people, at the same time the scores of Fl and MGD increased. Meanwhile, the score of OSDI in dry eye patients was significantly higher than that in non-dry eye individuals. The relative risk factors of dry eye were gender, age, wearing contact lens, long-time using of eye solutions, taking anti-allergy drugs.

CONCLUSIONS: The prevalence of dry eye in female is higher than that in the male. And the prevalence of dry eye increases following the aging process. Relative risk factors of dry eye are gender, age, wearing contact lens, long-time using of eye solutions, taking anti-allergy drugs.

Abstract: Lipocalin again... this time with sex steroid hormones

Human lipocalin-1 association with 3h-testosterone and 3h-estradiol.
Curr Eye Res. 2009 Dec;34(12):1042-9.
Crow JM, Nelson JD, Remington SG.
Department of Ophthalmology, HealthPartners Medical Group and Clinics, Regions Hospital, 640 Jackson Street, St. Paul, MN 55101, USA.

PURPOSE: Topical androgens and estrogens have been studied for use in treating ocular conditions such as dry eye. The aim of this study was to identify proteins from normal human tears that associated with exogenously added sex steroid hormones. One of the major proteins in ocular tears is lipocalin-1. It binds a variety of lipids and other hydrophobic molecules and is proposed to function as a carrier protein or a lipid scavenger.

METHODS: Normal human tears were incubated with (3)H-testosterone or (3)H-estradiol. Labeled tear proteins were separated on a Q Sepharose Fast Flow (QFF) Hi Trap strong anion exchange column with a step gradient of NaCl. (3)H-testosterone or (3)H-estradiol was measured in aliquots of eluted fractions using scintillation counts, and the remainder of each sample was gel electrophoresed and silver stained. In separate experiments, (3)H-steroid-labeled tear proteins were electrophoresed in 15% polyacrylamide gels and excised from the gels. Tritium content of the proteins was measured in a scintillation counter. Immunoblots with antibodies to lipocalin-1 verified the migration of lipocalin-1 in the gels.

RESULTS: (3)H-steroid labeled tear proteins were found in the 0.15 M NaCl fractions of QFF strong anion exchange columns. 18 kD lipocalin-1 (among other tear proteins) eluted in the 0.15 M NaCl fraction. Excision of labeled tear proteins from 15% polyacrylamide gels indicated that radioactive label was associated with an 18 kD protein. Immunoblots verified that lipocalin-1 migrated as an 18 kD protein.

CONCLUSIONS: The sex steroid hormones testosterone and estradiol associated with 18 kD lipocalin-1 in human tears.

Abstract: Protocol for an acupuncture trial

Very interesting - I don't recall coming across anything like this before. I would love to see the results of studies done with a protocol such as is described here. And as always I love to see OSDI included in the assessment methods.

Acupuncture for dry eye: a randomised controlled trial protocol.
Trials. 2009 Dec 3;10(1):112. [Epub ahead of print]
Kim TH, Kim JI, Shin MS, Lee MS, Choi JY, Jung SY, Kim AR, Seol JU, Choi SM.

BACKGROUND: Dry eye is usually managed by conventional medical interventions such as artificial tears, anti-inflammatory drugs and surgical treatment. However, since dry eye is one of the most frequent ophthalmologic disorders, safer and more effective methods for its treatment are necessary, especially for vulnerable patients. Acupuncture has been widely used to treat patients with dry eye. Our aim is to evaluate the effectiveness and safety of acupuncture for this condition.

METHOD: A randomised, patient-assessor blinded, sham (non-acupuncture point, shallow acupuncture) controlled study was established. Participants allocated to verum acupuncture and sham acupuncture groups will be treated three times weekly for three weeks for a total of nine sessions per participant. Seventeen points (GV23; bilateral BL2, GB4, TE23, Ex1 (Taiyang), ST1 and GB20; and left SP3, LU9, LU10 and HT8 for men, right for women) have been selected for the verum acupuncture; for the sham acupuncture, points have been selected that do not coincide with a classical acupuncture point and that are located close to the verum points, except in the case of the rim of the eye. Ocular surface disease index, tear film breakup time, the Schirmer I test, medication quantification scale and general assessment of improvement will be used as outcome variables for evaluating the effectiveness of acupuncture. Safety will also be assessed at every visit. Primary and secondary outcomes will be assessed four weeks after screening. All statistical analyses will be performed using analysis of covariance.

DISCUSSION: The results of this trial will be used as a basis for clarifying the efficacy of acupuncture for dry eye. Trial registration: NCT00969280.

Abstract: AS-OCT in measuring tear meniscus

[Application of anterior segment optical coherence tomography for measuring the tear meniscus height in the diagnosis of dry eye diseases]
Zhonghua Yan Ke Za Zhi. 2009 Jul;45(7):616-20.
[Article in Chinese]
Wang CX, Liu YZ, Yuan J, Li BB, Zhou SY.
The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

OBJECTIVE: To investigate the reproducibility and repeatability of anterior segment optical coherence tomography (AS-OCT) for measuring the tear meniscus height (TMH) and to evaluate its clinical application in the diagnosis of dry eye diseases.

METHODS: Evaluation of diagnostic test. The inferior tear meniscus height of 36 eyes of 36 patients with dry eyes and 38 eyes of 38 normal volunteers were measured by AS-OCT and slit lamp marker lens in Zhongshan Ophthalmic Center, Sun Yat-sen University from November 2007 to August 2008. Then the paired t test, intra-class correlation coefficiency test, ANOVA and Spearman test were used for comparing TMH values between normal subjects and dry eye patients, two different examiners, two analysts, the repeated examines within a week, and AS-OCT group and slit lamp reticle lens group.

RESULTS: There are no significant differences between different observers for the same 22 subjects [t = 1.881, P = 0.074; TMH: (0.256 +/- 0.052) mm and (0.265 +/- 0.066) mm], the same observer in different check-points for 20 subjects [ t = 1.306, P = 0.207; TMH: (0.265 +/- 0.056) mm and (0.272 +/- 0.052) mm] as well as different analyzers for the same 20 AS-OCT pictures [t = 2.048, P = 0.065; TMH: (0.266 +/- 0.059) mm and (0.259 +/- 0.062) mm]. There is a positive correlation between AS-OCT and reticule reading in measuring TMH (r = 0.713, P = 0.000); there are significant differences between normal subjects and patients with dry eye (t = 9.368, P = 0.000), and between groups of dry eye at different degree (F = 55.763, P = 0.000) [TMH: grade II, (0.228 +/- 0.036) mm; grade III, (0.145 +/- 0.056) mm; and grade IV, (0.084 +/- 0.048) mm]. The sensitivity and specificity of TMH value with AS-OCT for dry eye diagnosis was 77.8% and 71.7% when the diagnostic value was set to be 0.213 mm under the instruction of receptor operating characteristics curve (ROC).

CONCLUSION: AS-OCT has excellent reproducibility and repeatability for measuring the inferior tear meniscus height, and can be taken as an objective clinical imaging method for the diagnosis of aqueous deficiency dry eye.

Abstract: Anethol trithione

[The clinical therapic efficiency of anethol trithione on dry eye]
Zhonghua Yan Ke Za Zhi. 2009 Jun;45(6):492-7.
[Article in Chinese]
Wang H, Liu ZG, Peng J, Lin H, Zhong JX, Hu JY.

OBJECTIVE: To investigate anethol trithione therapic efficiency on dry eye. METHODS: It was a prospective random double-blind controlled study. Eighty cases diagnosed dry eye in Ocular Surface Out-patient Clinic of Xiamen University Affiliated Xiamen Eye Center from 2006 to 2008 were divided into two groups: anethol trithione group and control group, 40 cases in each group. Every group was then divided into two subgroups: weak dry eye subgroup,middle and severe dry eye subgroup. All groups had been added with 0.05% refresh drops. All patients had been detected and evaluated by subjective symptoms of dry eye, visual acuity, corneal fluorescent staining (F1), break-up time (BUT) and Schirmer I test (SIT) at pretherapy and 3, 7, 28 d of post-therapy. All groups had been compared and analyzed by F test and sample mean difference (SMD) or median difference (MD) comparison between pre-therapy and post-therapy. RESULTS: Except of tear and red eye,the other subjective symptoms of dry eye, Fl, BUT and SIT of weak dry eye subgroup of both groups had been improved at 7 d after therapy. Only those of middle and severe dry eye subgroup of anethol trithione group had been improved at 7 d after therapy compared with those of pretherapy: SMD = 0.96 (visual tiredness), 1.26 (dry and unsmooth sensation), 0.82 (foreign body sensation), 1.28 (burning sensation), 1.05 ( photophobia), 1.48 (pain); MD = 0.30 (visual acuity), 4.00 (Fl), 5.00 (BUT), 5.00 (SIT) [F = 15.30 (visual tiredness), 15.68 (dry and unsmooth sensation), 13.56 (foreign body sensation), 20.91 (burning sensation), 18.90 (photophobia), 27.22 (pain), 10.54 (visual acuity),188.21 (F1), 261.76 (BUT), 269.05 (SIT); P < 0.05]. Those of middle and severe dry eye subgroup of control group hadn't significantly been improved at 28 d after therapy: SMD = 0.10 (visual tiredness), 0.16 (dry and unsmooth sensation), 0.09 (foreign body sensation), 0.38 (burning sensation), 0.24 (photophobia), 0.36 (pain), 0.23 (red eye); MD = 0.10 (visual acuity), 0.50 (Fl), 0.50 (BUT), 0.50 (SIT) [F = 1.76 (visual tiredness), 1.61 (dry and unsmooth sensation), 1.02 (foreign body sensation), 2.39 (burning sensation), 2.42 (photophobia), 2.73 (pain), 2.55 (red eye), 1.46 (visual acuity), 2.35 (Fl), 2.90 (BUT), 2.76 (SIT); P > 0.05]. SIT of anethol trithione group had been improved more significantly after therapy (F = 13.77, P < 0.05). CONCLUSION: Anethol trithione could significantly improve middle and severe dry eye patients' symptoms and signs whose lacrimal gland function survival and it has clinical application value.

Abstract: Tear lipocalin & lipids

Tear Lipocalin Captures Exogenous Lipid from Abnormal Corneal Surfaces.
Invest Ophthalmol Vis Sci. 2009 Dec 3. [Epub ahead of print]
Glasgow BJ, Gasymov OK, Abduragimov AR, Engle JJ, Casey RC.
The Jules Stein Eye Institute - UCLA, Department of Ophthalmology, Los Angeles, United States.

Purpose: The cornea is protected by apical hydrophilic transmembrane mucins and tears. In pathologic states the mucin barrier is disrupted creating potential for meibomian lipids to adhere more strongly. Undisplaced lipids create an unwettable surface. The hypothesis that pathologic ocular surfaces alter lipid binding and the ability of tear proteins to remove lipids was tested. Methods: Corneas with pathologic surfaces were studied for lipid adhesion and removal by tears. Capture of fluorescent labeled phospholipids by human tears was assessed by steady state fluorometry. Tear proteins were separated by gel filtration chromatography and analyzed for bound lipids. Results: Contact angle measurements reveal strong lipid adherence to corneas submerged in buffer. Lower contact angles are observed for lipids on completely de-epithelialized versus intact corneas (p=0.04). Lipid removal from these surfaces is greater with whole tears than tears depleted of tear lipocalin (p<0.0005). Significantly less lipid is captured by tears from Bowman's layer than from epithelial bearing surfaces (p<0.025). The only tear component to bind the fluorescent tagged lipid is tear lipocalin. The histology of a rare case of dry eye disease demonstrates the dominant features of the contemporaneous bullous keratopathy. Lipid sequestration from this cornea by tear lipocalin was robust. Conclusions: Lipid is captured by tear lipocalin from corneas with bullous keratopathy and dry eye. Lipid removal is slightly abrogated by greater lipid adhesion to Bowman's layer. Reduced secretion of tear lipocalin documented in dry eye disease potentially could hamper lipid removal and exacerbate ocular surface pathology.

Abstract: Inputs and outputs of the lacrimal system

Inputs and outputs of the lacrimal system: review of production and evaporative loss.
Ocul Surf. 2009 Oct;7(4):186-98.
Tomlinson A, Doane MG, McFadyen A.
From Vision Sciences, Glasgow Caledonian University, Glasgow, UK.

Meta-analyses were carried out of studies of tear production (by fluorophotometry, tear turnover rate[TTR]) and evaporation (from capture of fluid loss from the eye). TTR was reduced in dry eye relative to normal at 9.26 +/- 5.08%/min (0.54 +/- 0.28 mul/min) vs 16.19 +/- 5.1%/min (1.03 +/- 0.39 mul/min); with values of 7.71 +/- 1.02 %/min (0.4 +/- 0.10 mul/min) in aqueous deficiency dry eye (ADDE) and 11.95 +/- 4.25%/min (0.71 +/- 0.25 mul/min) in evaporative dry eye (EDE). Evaporation was increased in dry eye at 21.05 +/- 13.96 x 10(-7)g/cm(2)/s (0.21 +/- 0.13 mul/min) vs 13.57 +/- 6.52 x 10(-7)g/cm(2)/s (0.14 +/- 0.07 mul/min) in normals; with values of 17.91 +/- 10.49 x 10(-7)g/cm(2)/s (0.17 +/- 0.1 mul/min) in ADDE and 25.34 +/- 13.08 x 10(-7)g/cm(2)/s (0.26 +/- 0.16 mul/min) in EDE. Evaporation rate from tear film thinning was also considered, and possible reasons and consequences for the much higher rates thereby reported are discussed. A new statistical approach determined diagnostic efficacy of cut-offs for dry eye derived from the meta-analyses; sensitivities and specifications ranging from 69.5 to 98.6% and 58.7 to 96.8% (TTR) and 45.5 to 61.2% and 79.8 to 90.6% (evaporation). Indices of tear dynamics were reconsidered, and ratios of evaporation and TTR suggest that an increase of between 2 and 3 times may be associated with dry eye.

Abstract: Signs vs. Symptoms

Summary of a literature review on the topic of the well-known (well, to us anyway) baffling discrepancies between what the doctor sees under the slit-lamp and how the patient feels. We are going to see more and more studies and healthy debate on this topic in the near future I believe. And we need it.

The association between symptoms of discomfort and signs in dry eye.
Ocul Surf. 2009 Oct;7(4):199-211.
Johnson ME.
From the Department of Ophthalmology, Bristol University, Bristol, UK.

ABSTRACT There is an intuitive causal link between the signs of dry eye observed by clinicians and the severity of symptoms experienced by patients. However, this expectation is challenged by asymptomatic patients with obvious tear film anomalies and extensive ocular surface compromise and, conversely, by patients with intolerable symptoms of dryness in whom only minimal disease can be observed. Knowledge of how symptoms reflect the state of disease would enable clinicians to better understand and manage patients with apparently idiosyncratic disease presentations. This paper reviews the literature and describes the difficulties of investigating the correspondence between symptoms and signs in dry eye. The measurement of and analytical methods used to compare these two clinical areas are discussed. Theoretical aspects of the relationship between symptoms and signs are also covered. Typically, a positive relationship exists between the severity of symptoms and objective tests in dry eye, but, on balance, data suggest that the association between symptoms and the majority of these tests is not strong; thus, the power of predictive inference of one from knowledge of the other is low. Firm conclusions cannot be made on the nature of the relationship at this time because of limitations in our ability to measure either individually.

Abstract: Modeling tears (or parts thereof)

Interesting one for those of you following tear osmolarity.

A mass and solute balance model for tear volume and osmolarity in the normal and the dry eye.
Prog Retin Eye Res. 2009 Nov 26. [Epub ahead of print]
Gaffney EA, Tiffany JM, Yokoi N, Bron AJ.
Centre for Mathematical Biology, Mathematical Institute, University of Oxford, UK; Oxford Centre for Collaborative Applied Mathematics, Mathematical Institute, University of Oxford, UK.

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye. The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity. Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable

Abstract: Demodex and chronic blepharitis

Just a case study, but thought it might be of interest to those following the Demodex connection potential.

[Chronic blepharitis: which role for Demodex folliculorum? A case report.]
Ann Biol Clin (Paris). 2009 Nov-Dec;67(6):701-4.
[Article in French]
Martinaud C, Gaillard T, Pons S, Fournier B, Brisou P.
Service de dermatologie, Fédération des laboratoires HIA Sainte Anne, Toulon.

We present a 73-year-old woman presented to our hospital with a 2 years history of eyes itching. The ophthalmological testing was normal. Physical examination revealed blepharitis and lesions acnea-like on mouth, nose and chest. Biological testing revealed no abnormalities. Histologic study and direct immunofluorescence on a cutaneous biopsy were no contributive. The research of an allergic origine was practised by cutaneous and serological tests and negative. An examination of eyelashes was performed and yielded Demodex. Demodex folliculorum is a mite that is the most common permanent ectoparasite of humans, which is thought to be linked to blepharitis and allergic blepharoconjunctivis with rosacea, although much controversy persists. Recent studies demonstrate a high frequence of chronic blepharitis when Demodex are abundant. Several molecules can be used to treat this infestation. Parasiticide as oral ivermectine may be useful when the infestation is important.

Abstract: MGs part III and IV

[Meibomian glands : part III. Dysfunction - argument for a discrete disease entity and as an important cause of dry eye]
Ophthalmologe. 2009 Nov;106(11):966-79.
[Article in German]
Knop E, Knop N, Brewitt H, Pleyer U, Rieck P, Seitz B, Schirra F.
Forschungslabor der Augenklinik, Charite - Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK), Ziegelstrasse 5-9, 10117, Berlin, Deutschland.

Meibomian gland dysfunction (MGD), mainly synonymous with posterior blepharitis but typically without prominent inflammatory alterations of the lid margin, is a discrete disease entity and a frequent cause of wetting deficiencies of the ocular surface leading to dry eye disease that deserves increased recognition by clinicians. The history, classification, pathology, influencing factors, diagnostics and therapy are explained and discussed. MGD is mainly based on an obstructive mechanism caused by hyperkeratinization of the excretory duct and/or increased viscosity of the secretion (meibum) with subsequent deficiency of the tear film lipid layer. MGD is influenced by the hormonal status and by chemical and mechanical noxes as well as genetic defects and it occurs more frequently in women and generally increases with age. It results in stasis of meibum inside the glands, dilatation of the ductal system and eventually in atrophy and loss of glandular tissue (gland dropout). Careful investigation of the eyelids and lid margins with eversion, if necessary, should therefore be performed in every case of a wetting defect, notably before fitting contact lenses. Particularly important is the inspection of the meibomian orifices and diagnostic expression by mild mechanical compression of the lid.

[Meibomian glands : part IV. Functional interactions in the pathogenesis of meibomian gland dysfunction (MGD)]
Ophthalmologe. 2009 Nov;106(11):980-7.
[Article in German]
Knop E, Knop N.
Forschungslabor der Augenklinik, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Ziegelstrasse 5-9, 10117, Berlin, Deutschland.

Obstructive dysfunction of the meibomian glands (MGD) is surprisingly frequent in the general population and increases with age. Clinically, the focus is mainly on the consequences at the ocular surface in the sense of an evaporative dry eye syndrome. However, in addition, chronic obstruction of the meibomian glands also leads to degeneration of the secretory gland tissue which can result in a secondary hyposecretion even if the primary obstruction is later resolved by therapeutic approaches.Important influencing factors in the pathogenesis of obstructive MGDs and their interaction during the progression of the disease are systematically analyzed and displayed in a flow diagram. Age, hormonal disturbances and environmental influences, such as contact lenses, as well as qualitative alterations in the composition of the meibomian oil (meibum) lead to hyperkeratinization of the ductal epithelium and increased viscosity of the meibum which result, either alone or in combination, in obstruction of the duct and orifice. This leads to a lack of meibum on the lid margin and tear film with downstream hyperevaporative dry eye syndrome. At the same time, obstruction leads to a stasis of meibum inside the meibomian gland with increased pressure and resulting dilatation of the ducts and in atrophy of the acini with rarefaction of the secretory meibocytes and gland dropout. Stasis can also increase the growth of commensal bacteria, their production of oil degrading enzymes (lipases) and release of toxic mediators. These factors can, in return, act as self-enforcing feedback loops in the sense of vicious circles that aggravate the primary hyperkeratinization and compositional disturbance of meibum and can hence lead to a progressive MGD.

Abstract: Sex hormones & dry eye

For those of you (doctors) who have access to this and read German :-) I would love to be able to read this literature review of thinking on sex hormones and dry eye.

[Sex hormones and dry eye]
Ophthalmologe. 2009 Nov;106(11):988-94.
[Article in German]
Schirra F, Seitz B, Knop N, Knop E.
Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes, UKS, Kirrberger Str. 1, 66421, Homburg/Saar, Deutschland.

Among ophthalmic diseases dry eye in its various forms, represents an entity with one of the highest prevalences and at the same time the lowest chance for causal therapy. Since some years there is growing evidence that sex hormones play a key role in the formation and course of the disease and thus provide potentially promising approaches for therapy. The objective of this article is to briefly outline current scientific knowledge on the relationship between androgens, estrogens,and progesterones on the one hand and the lacrimal gland and Meibomian glands respectively.

Abstract: Dry eye in Jeddah, Saudi Arabia

I don't know what to make of this. I mean, I know it's dry there, but....

Or, is accompanying someone to the eye doctor a risk for dry eye in Jeddah?

Prevalence of dry eye in the normal population in Jeddah, Saudi Arabia.
Orbit. 2009;28(6):392-7.
Bukhari A, Ajlan R, Alsaggaf H.
Department of Ophthalmology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

PURPOSE: To estimate the prevalence of dry eye disease in the normal non-complaining population.

METHODS: Prospective systematic random sampling study of 251 subjects who accompanied patients with appointments to the eye clinic. Interviewers administered a dry eye symptoms and risk factor questionnaire. Tear film break up time, fluorescein corneal staining and Schirmer's test were performed. Slit lamp examination to evaluate the lid margins, Meibomian glands and ocular surface structures was also performed.

RESULTS: Dry eye was diagnosed in 234 (93.2%) subjects on the basis of presence of one or more symptoms occurring often or most of the time, together with one or more of the following signs: tear film break up time < or = 10 seconds, fluorescein corneal staining > or = grade 1 and Schirmer test score < or = 5 mm. There was no statistically significant association between dry eye with advancing age or gender. Blepharitis was detected in 215 (91.9%) of the dry eye cases. Smoking was found to be the second most common risk factor as 18.8% of the dry eye cases were smokers. Sicca syndrome was found in 24.4% of the subjects.

CONCLUSION: Dry eye is very prevalent disease. Blepharitis was found to be very common among dry eye cases. There was no statistically significant association between dry eye and age or gender in our study population

Abstract: Vesicare and dry eye side effects

I have really been appreciating that more trials of non-eye drugs have been evaluating and reporting dry eye side effects. Here's one for a drug for overactive bladder.

Effects of solifenacin on overactive bladder symptoms, symptom bother and other patient-reported outcomes: results from VIBRANT - a double-blind, placebo-controlled trial.
Int J Clin Pract. 2009 Dec;63(12):1702-14.
Vardy MD, Mitcheson HD, Samuels TA, Wegenke JD, Forero-Schwanhaeuser S, Marshall TS, He W.
Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, NY 10463, USA.

AIM: The aim of this study was to evaluate the efficacy of solifenacin on symptom bother using the Overactive Bladder Questionnaire (OAB-q).

METHODS: In VIBRANT, a double-blind, US-based trial, patients with OAB for > or = 3 months received flexibly dosed solifenacin or placebo for 12 weeks. At baseline and 4-week intervals, patients completed the OAB-q [symptom bother and health-related quality of life (HRQL) scales] and 3-day bladder diaries; other patient-reported outcome measures were also assessed at baseline and week 12. The primary efficacy end-point was the change from baseline to end of treatment (EOT) on the OAB-q Symptom Bother scale. Adverse events (AEs) were monitored.

RESULTS: At EOT, solifenacin (n = 377) vs. placebo (n = 374) significantly improved mean symptom bother (-29.9 vs. -20.4, p < 0.0001), HRQL total (25.3 vs. 16.7, p < 0.0001) and all HRQL domain scores (Ps < 0.0001). Solifenacin vs. placebo significantly improved daily episodes of urgency, incontinence and frequency but not nocturia. Significant separation from placebo was evident as early as week 4. Overall, significantly more solifenacin vs. placebo patients reported treatment benefit (84% vs. 63%), satisfaction (80% vs. 59%) and willingness to continue (79% vs. 60%; Ps< 0.0001). Treatment-related AEs in solifenacin vs. placebo patients were dry mouth (13% vs. 2%), constipation (8% vs. 2%) and dry eye (2% vs. 0.3%).

CONCLUSIONS: As early as week 4 and through EOT, flexibly dosed solifenacin significantly improved OAB symptom bother and HRQL as well as the symptoms of urgency, frequency and incontinence compared with placebo. Significantly more solifenacin patients reported treatment benefit and satisfaction at week 12 compared with placebo.

Abstract: Tear meniscus volume following punctal occlusion

More evidence in favor of plugs. Sort of. Collagen plugs increase tear meniscus if you're dry, don't if you're not; do not affect Schirmer score if you're dry, actually lower it if you're not dry. Hm.

Tear meniscus volume in dry eye following punctal occlusion.
Invest Ophthalmol Vis Sci. 2009 Nov 20. [Epub ahead of print]
Chen F, Shen M, Chen W, Wang J, Li M, Yuan Y, Lu F.
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, China.

Purpose: To use optical coherence tomography (OCT) to evaluate the effect of punctal occlusion on tear meniscus volume in dry eye patients.

Methods: Occlusion of both upper and lower puncta with collagen plugs was performed on one eye of 20 dry eye patients and 20 normal subjects. The upper and lower tear menisci were imaged simultaneously by real-time OCT before punctal occlusion and repeated on days 1, 4, 7 and 10 afterwards. The heights, cross-sectional areas, and volumes of the menisci were obtained. Schirmer I test with anesthesia and tear break-up time (TBUT) were also performed.

Results: At baseline, both upper and lower tear meniscus heights and volumes in dry eye patients were smaller than those in controls (P < 0.05). The lower tear meniscus volume was 0.28 +/- 0.09 mul in dry eye patients and 0.55 +/- 0.22 mul in controls at baseline (P<0.05). After punctal occlusion, the Schirmer I test scores of dry eye patients did not change (P>0.05), but the heights and volumes of both upper and lower tear menisci increased (P<0.05). In control subjects, Schirmer I test scores decreased (P<0.05), but heights and volumes of both upper and lower tear menisci did not change (P>0.05).

Conclusion: Punctal occlusion induced increases of both upper and lower tear meniscus volumes in dry eye patients. The absence of change in the tear menisci of control eyes may indicate the presence of an auto-regulatory mechanism in the tear system for maintaining a balance of tear volume.

Saturday, December 5, 2009

Abstract: Smartplugs, canaliculitis & plug removal

Prevalence of canaliculitis requiring removal of SmartPlugs.
Ophthal Plast Reconstr Surg. 2009 Nov-Dec;25(6):437-9.
Prevalence of canaliculitis requiring removal of SmartPlugs.
Hill RH 3rd, Norton SW, Bersani TA.

PURPOSE: To report the first accurate prevalence of canaliculitis associated with the use of the SmartPlug.

METHODS: All patients from a single private ophthalmology practice who received SmartPlugs from 2002 to 2007 were identified. All patients from the private ophthalmology practice that developed canaliculitis secondary to SmartPlug insertion were referred to a single private ophthalmic plastic and reconstructive surgery office. A retrospective review of those 17 patients was performed.

RESULTS: From 2002 to 2007, a total of 235 patients were identified from a single private ophthalmology practice with a total of 402 SmartPlugs inserted. Of those 235 patients, 17 developed canaliculitis and were referred to a single private ophthalmic plastic and reconstructive surgery office. The prevalence of canaliculitis per patient was 7.23%. The prevalence of canaliculitis per SmartPlug inserted was 4.73%. The average time from SmartPlugs insertion to onset of symptoms was 3 years. All affected patients required canaliculotomy and plug removal.

CONCLUSIONS: This is the first study reporting the prevalence of canaliculitis associated with the use of the SmartPlug. All affected patients required surgical intervention, after which many continued to have dry eye and one required bilateral Jones tubes. Ophthalmologists using the SmartPlug for the treatment of dry eye syndrome should carefully weigh the risks and benefits of their use.

Thursday, December 3, 2009

Moorfields' new dry eye site

UK users... Moorfields recently launched a new website dedicated to dry eye.

Dry Eyes Medical

Nothing spectacular as dry eye websites go, but all the same it's nice to see UK resources and attention to dry eye expanding. In treatments, it mentions moisture chambers and sclerals which most sites of similar superficiality don't.

Treating MGD early

There was an interesting 'panel' discussion on PCON recently about whether to treat lid margin disease (MGD) in patients who do not yet have symptoms (don't hurt). I'm posting some highlights here because I think this is a very timely topic. While I'm not sure I'm crazy about the idea of them prescribing all these drugs to people with a very mild case, on the other hand the fact that they are identifying the signs and educating their patients about it absolutely thrills me. That's surely a sign of significant progress. This is not, obviously, knowledge diffused evenly through optometric circles, else we would not still be hearing so frequently from people with raging lid margin disease who were not properly diagnosed, let alone treated, by their first four doctors. But progress leads to more progress.

Panel: Treating asymptomatic lid disease improves comfort, long-term results

We now understand the profound influence of adequate meibomian gland secretions on ocular comfort and quality of vision.
(Dr. William Townsend)

Define "we", please? :-)

Perhaps this could be rephrased as "We all ought to, and a growing number of us actually do now understand..."

We treat all patients with active meibomian gland dysfunction to prevent ongoing inflammation and tissue damage. Therapeutic modalities such as warm compresses, lid expression, systemic tetracyclines, oral omega-3 essential fatty acids and cyclosporine A have been shown to positively affect meibomian gland disease. While the immediate benefits of therapy such as increased gland output and visual enhancement are desirable, the real benefits of long-term therapy (preserving meibomian gland function and preventing atrophy) are the real effects that the patient will appreciate years later.

The management of lid disease is particularly challenging because although the provider may recommend appropriate treatment, the task of carrying out the administration of the various therapies falls on the patient. Early detection and treatment may save him or her from the discomfort and annoyance of advanced meibomian gland disease years later.
(Dr. William Townsend)

Currently, AzaSite, as well as Restasis, is an off-label treatment option for blepharitis and meibomianitis. However, with evidence growing that drugs such as these are proving beneficial and offering our patients an actual treatment vs. palliative care, I have begun prescribing treatment to previously asymptomatic patients. My “go to” treatment plan includes the standard warm compresses and lid hygiene (preferably with some type of commercial lid scrub) and AzaSite twice daily for 2 days and then once daily for the next few weeks. It is the treatment plan I put myself on.
(Dr. Blair Lonsberry)

When I treat asymptomatic patients with signs of blepharitis, I take the basic philosophical approach that no patient ever starts with severe lid margin disease. Most patients start with a mild case that, left untreated, progresses to more severe forms. That being said, I explain to patients with lid margin disease that an infection or inflammation of the lid margin left untreated can progress to significant symptoms that include itching, burning, chronic redness and uncomfortable contact lens wear and that it can also make other conditions such as dry eye worse. After a thorough explanation most patients decide to pursue treatment.
(Dr. Scot Morris)

Patients are not always as asymptomatic as they seem at first glance. Asymptomatic and completely satisfied are two different things. I ask patients about dryness, contact lens wearing time and red eyes. I always discuss my findings, as well as the risks of doing nothing and benefits of treatment.

Foaming eyelid cleansers, such as OcuSoft Lid Scrub Foaming Eyelid Cleanser (OcuSoft, Rosenberg, Texas) make it easy for patients to treat mild blepharitis in the shower. It is surprising how many asymptomatic patients return much happier, simply with a minimal routine change.
(Dr. Christine Sindt)

Heading to Boston at last

Aaaaaah. I have been trying to work in a trip to Boston Foundation for how many months now? Finally, finally it has worked out. Leaving Sunday, returning Wednesday with brand new eyeballs. Well, not quite that, but new prostheses (did you know sclerals are actually prosthetic devices?). Hurray, hurray.

MG Expressor Kit

...And in that same EyeWorld article, there was mention of a new kit for doctors to express those glands for the rest of us. Personally I don't see why a kit's needed (rice anyone? and fingers?) but hey, the more medical devices around for it the more doctors will, hopefully, be learning about the need to be conversant in meibomian gland manipulation. WAKE UP, DOCTORS. The population is aging. MGD is booming. Patients are shopping around for doctors on the basis of how meibomianitis literate they are. Are you? And by the way, stock analysts care about dry eye. Do you? Well, OK, if you're reading this blog you probably do. Maybe you could forward a link to a colleague who doesn't... yet.

For less severe cases of meibomian gland dysfunction, Mario Gutierrez, OD, FAAO, has developed the MG Expressor Kit (Gulden Ophthalmics), which combines the traditional therapies of warm compresses and massage, though in a more rigorous form. The kit includes a gel mask that can be warmed, the expressor tool and sanitary caps that can be placed over the roller. Dr. Gutierrez described the technique.

“Once the lids are warm, it liquefies the contents of the meibomian glands,” he told PCON. “Then, we basically roll the tool on the eyelid near the eyelid margin, and that helps express the liquefied meibomian gland content.

“I typically warm up the eyelids, use the roller, really work the nasal eyelids — the glands — a little bit more,” he continued. “This seems to help the patient become less symptomatic if we can get the nasal meibomian glands working well. Then I’ll go back and warm the lids a little bit more, maybe for a minute or two more, and then go back and roll it one more time to try and liberate as much of the expressions as possible.”

According to Daniel Adams, OD, the expressor is best used at a horizontal angle, working from the lash line upwards.

“The gel pack should only be used for 3 minutes to warm the glands, and then the expressor tool should be rolled horizontally — not vertically — over the eyelid, forcing the meibum upwards,” Dr. Adams said in an interview. “You want to soften the oil that’s congealed in the gland, and once you are able to get it to a ‘soft butter’ stage, roll the glands and try to express it out.”

Maskin probe

Noticed all the buzz lately about the new Maskin probe?

EyeWorld discussed it in a recent article about "aggressive" (i.e. beyond doxy, azasite and classic compress/scrub routines) treatments for meibomian gland dysfunction.

The Maskin Meibomian Gland Intraductal Probe (Rhein Medical), developed by Steven L. Maskin, MD, helps remove obstructions within the duct. Dr. Maskin told Primary Care Optometry News that clinicians can enter the meibomian gland with the probe and provide “dramatic and immediate” relief to patients.

Blockages within the gland may be caused by fibrovascular tissue that grows into the duct with new blood vessel formation as well as an abnormal hyperplastic keratinized ductal epithelium or scarring in or over the orifice, he said.

“What I found when I entered the meibomian gland was that there was frequently some resistance deeper inside, within the duct, which was able to be relieved with mild pressure,” Dr. Maskin said. “When you apply that pressure, you’ll be able to penetrate through that and there will be a ‘pop’ characteristic of a fibrovascular membrane. You can create a patent open duct from orifice to the deeper duct. Patients’ lid tenderness dramatically and immediately improves.”

...But wait, lest you interpret my "beyond doxy, azasite, etc", bear in mind that it's probably in addition, not instead of:

...Marguerite McDonald, MD, shared her protocol with PCON. She first holds lidocaine gel against the lid margin to anesthetize the area where the probe will be inserted. Afterward, she prescribes a combination of topical and sometimes oral medications to treat the disease.

“For patients with moderate to severe meibomian gland disease, I place them on ‘soaks and scrubs’ twice daily, as well as on AzaSite (azithromycin 1%, Inspire), one drop in both eyes twice daily for 2 days followed by one drop daily for at least a month,” she said. “Some severe patients stay on AzaSite indefinitely.

“I ask the patients to rub the drop into the base of their lashes for a few seconds while their lids are gently closed, immediately after instilling the drop,” she continued. “In addition, many patients are placed on oral doxycycline (100 mg) twice daily for a week to 10 days, then 20 mg once daily for a few months, if not indefinitely.”

And of course, on DryEyeTalk it's been a subject of discussion for some months past, as in this thread.

Dropless ad

Have you seen the Lacrisert "Dropless" ad?

I can't post it because their site doesn't let you pinch its pix, but it's a shot of a comely and presumably 50yo+ lady with the photo cut off just below her shapely, bare shoulders. The text says "Freedom to go dropless."

In the staid world of ophthalmic pharmaceutical advertising where edgy means snapping a photo of the bottle from a new and different angle and progressive Restasis commercials are showing up on websites like, I thought it was pretty cute.

Thursday, November 19, 2009

Abstract: The life and times of... normal meibomian glands

The Diurnal Secretory Characteristics of Individual Meibomian Glands.
Cornea. 2009 Nov 11.[Epub ahead of print]
Blackie CA, Korb DR.
From the *Korb Associates, Boston, MA; and daggerTearScience, Inc, Morrisville, NC.

PURPOSE:: To investigate the diurnal secretory characteristics of individual meibomian glands (MGs).

METHODS:: Ten subjects (4 females and 6 males) with healthy eyelid appearance and without dry eye symptoms were recruited (mean age = 23.8 +/- 1.8 years). Both right and left lower eyelids were marked in 3 places to locate 5 consecutive MGs in each third (temporal, central, and nasal) of the lower eyelid. A total of 15 MGs per eye were diagnostically expressed for 10 seconds on both right and left lower eyelids every 3 hours for 4 consecutive measurements over a 9-hour period.

RESULTS:: Thirty-four percent of all tested MGs yielded liquid secretion at all measurements. Sixty-nine percent of the tested nasal MGs yielded liquid secretion at all measurements in contrast to 31% of the central MGs and only 22% of the temporal MGs. The mean numbers of MGs secreting liquid oil were significantly higher in the nasal section relative to the central and temporal sections at all measurements (p < 0.001, all measurements).

CONCLUSIONS:: (1) A single MG is capable of secreting oil on demand over the course of a working day ( approximately 9 hours); (2) nasal MGs were the most likely to secrete upon demand over the course of day compared with the temporal and to a lesser degree the central MGs; and (3) secretory characteristics of individual MGs examined as a function of their location in the lower eyelid does not change diurnally.

Abstract: KLAL in LSCD

Long-term outcomes of keratolimbal allograft for total limbal stem cell deficiency using combined immunosuppressive agents and correction of ocular surface deficits.
Arch Ophthalmol. 2009 Nov;127(11):1428-34.
Liang L, Sheha H, Tseng SC.

OBJECTIVE: To determine the long-term outcomes of keratolimbal allograft (KLAL).

METHODS: Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP.

RESULTS: More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 microg/mL (SD, 0.6 microg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period.

CONCLUSION: Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Abstract: Topical naltrexone

Not all that relevant to our crowd (most of us would rather have a decrease rather than increase in corneal sensitivity!) but interesting nonetheless.

Dry eye reversal and corneal sensation restoration with topical naltrexone in diabetes mellitus.
Arch Ophthalmol. 2009 Nov;127(11):1468-73.
Zagon IS, Klocek MS, Sassani JW, McLaughlin PJ.

OBJECTIVE: To determine if topical application of naltrexone hydrochloride (NTX), an opioid antagonist, restores tear production and corneal sensation in rats with diabetes mellitus.

METHODS: Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10(-5)M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only.

RESULTS: Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle.

CONCLUSION: Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats.

CLINICAL RELEVANCE: Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.

Abstract: Stem cell transplantation

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye.
Bone Marrow Transplant. 2009 Nov 9.
Wang Y, Ogawa Y, Dogru M, Tatematsu Y, Uchino M, Kamoi M, Okada N, Okamoto S, Tsubota K.
[1] Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan [2] Department of Ophthalmology, The Eye and ENT Hospital of Fudan University School of Medicine, Shanghai, China.

We evaluated ocular surface alterations in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with or without chronic GVHD-related dry eye in a prospective study. Fifty eyes of 25 post-HSCT patients and 28 eyes of 14 age-matched healthy controls were included. Meibomian gland (MG) obstruction, tear evaporation rate, corneal sensitivity (CS), Schirmer test-I, tear break-up time (BUT) and ocular surface vital staining were examined. Conjunctival impression and brush cytology specimens were collected to evaluate the goblet cell density (GCD) and the inflammatory cell numbers. Obvious MG obstruction, decreased CS and enhanced tear evaporation rate were found in post-HSCT patients compared with normal controls. In addition, decreased conjunctival GCD, increased conjunctival squamous metaplasia and inflammatory cells were noted in cGVHD-related dry eyes compared with normal controls and post-HSCT without dry eye subjects. Furthermore, the conjunctival inflammatory cells were significantly higher in severe dry eyes compared with mild dry eyes (P=0.03). We found comprehensive ocular surface alteration in post-HSCT patients, regardless of whether they had cGVHD-related dry eye or not. The results suggest that the extent of inflammatory process seems to have a pivotal role in the outcome of the cGVHD-related dry eye.

Monday, November 16, 2009

Abstract: Aussie study on McMonnies questionnaire

McMonnies Questionnaire: Enhancing screening for Dry Eye Syndromes using Rasch Analysis.
Invest Ophthalmol Vis Sci. 2009 Nov 5.
Gothwal VK, Pesudovs K, Wright T, McMonnies C.
NH&MRC Centre for Clinical Eye Research, Department of Ophthalmology, Flinders Medical Centre and Flinders University of South Australia, Adelaide, Australia.

PURPOSE: To determine, using Rasch analysis, if the McMonnies questionnaire satisfied the properties of a measure and whether screening for dry eye syndromes (DES) could be enhanced using different scoring approaches.

METHODS: The questionnaire was self-administered by 43 female Sjögren syndrome patients (>45 years) recruited from a specialized rheumatology clinic and 140 age-matched controls. Data were scaled using Rasch analysis and assessed for response category behavior and ability to reliably discriminate between severity of participant's dry eye symptoms (i.e. person separation reliability; minimum acceptable value 0.80). Standard summary statistics of screening performance were calculated for raw and Rasch-scaled scores from Receiver-Operating Characteristic analysis including area under the curve (AUC). Best predictors (i.e. questions) from a discriminant analysis were used to calculate a discriminant function for both Rasch-scaled and raw scores.

RESULTS: Response categories were not used as intended, necessitating collapse of categories. Person separation reliability was inadequate (0.75). Rasch-scaled discriminant cut-off score of -2.29 logits from 7 items provided an AUC of 0.99 with 95% sensitivity. However, discriminant raw score from modification in the scoring of a question, i.e. use of medications (used singly rather than individual questions) provided AUC (0.97) not significantly different (z = 1.11, p = 0.27) with 98% sensitivity and required only 2 questions.

CONCLUSIONS: In this population, the McMonnies questionnaire does not function as a measure. However, various scoring methods can be used to efficiently screen for DES.

Thursday, November 12, 2009

And while I'm on the subject

I finally got around to tasting the pomegranate-blueberry Vegan Total Omega swirl this morning. Somehow it just didn't quite sound like my type of product. But wow! I think I like that one just as much as the strawberry-banana flaxseed oil one... hm, maybe even more. Most definitely worth it. But then, I get free samples from the manufacturer so it's easy for me to say. If this was coming out of my actual, gerk, budget, I'd definitely stick with strawberry banana.

Oh, and my daughter insisted on testing both this and the Chocolate Raspberry one to make sure "kids don't die of it". Her approval rating as measured in probability of stretch marks from smiling too wide was pretty near the top of the scale.

Barleans chocolate-raspberry Omega 3 swirl... update.

I have never liked chocolate "flavored" things. I even remember when as a kid I got conned into trying so-called chocolate flavored fluoride at the dentist, which was utterly revolting. When it comes to chocolate, I want the real thing or nothing at all. Whoops... I forgot... the chocolate swirl actually does have real chocolate. But still! At the end of the day it's really just an attempt to cover up something you wouldn't otherwise like, right?

Well, yes, but as long as it does so successfully, I guess it's not a crime.

So I tried it, finally, last night.

Would you believe, it was actually pretty darned good. In color, it's just slightly lighter than Hershey's syrup, and in consistency, a tad thicker. In the mouth... The first single drop I was ambivalent about. I moved up to half a spoon. "He likes it! Hey Mikey!". I racked my brain trying to figure out what it reminded me of and I finally decided on a dark chocolate filled with raspberry cordial. Now, obviously, you're going to notice the difference between this and the real thing! But as a cover-up, I think this is a win.

Where does it rank? Well, for me personally, I'd say it ranks above Lemon Zest fish oil swirl and below Strawberry-Banana flaxseed oil swirl. I'm going to keep this one in the fridge as a "for variety's sake" product.

Almost forgot... here's a link for more details.

Monday, November 9, 2009

Omega 3 in (gulp!) CHOCOLATE

Would you believe it?

Trust Barleans to come up with something like this. Their Omega Swirls (flavored Omega 3s smoothie-style that you can take off a spoon without 'drinking oil') have been such a hit across the country that they've been expanding the product line.

The latest is "Essential Woman" - a Chocolate-Raspberry (made with real chocolate...) supplement with organic flaxseed oil, evening primrose oil and lignans.

I haven't tried it yet... I'll let you know when I get a taste!

New products: Firm date on Quartz

The new QUARTZ will be ready to ship on Thursday, November 12th.

I don't have any pictures yet - sorry. Here is a picture of the Onyix... picture this made of a CLEAR material. Onyix and Quartz are foamless slim silicone shields for night eye protection.

Here's a link to Quartz in the Dry Eye Shop.

I am excited about this one. The only other clear night products I'm aware of are post-LASIK style goggles and they are not made to last (nor are they terribly comfortable or effective) and the very costly disposable clear shields from Medtronic. This one is going to be great for a lot of niche uses, including elderly folks at risk of falls in the night. And while it does fog, in my personal testing of it, it's not too much of a stretch to imagine you could do some bedtime reading with it on. I've even used it while typing at the computer.

Friday, November 6, 2009

Drug news: Inspire's Prolacria, Azasite clinicals fully enrolled

Inspire Completes Patient Enrollment in Three Late-Stage Clinical Trials in Cystic Fibrosis, Dry Eye and Blepharitis

DURHAM, N.C.--(Business Wire)--
Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today patient enrollment
is complete in three of its late-stage clinical trials.

"We are pleased to be executing on our strategic plan with the achievement of
these patient enrollment milestones in the clinical development programs for
denufosol, PROLACRIA and AZASITE®,as this places us in a position to have
top-line results from all our late-stage clinical programs within 18 months. We
would like to thank the dedicated clinical investigators, study coordinators and
patients who participated in our trials as well as the Cystic Fibrosis
Foundation and its affiliates for raising awareness of the importance of
participating in clinical trials," stated Benjamin R. Yerxa, Ph.D., Executive
Vice President and Chief, Research and Development.

Abstract: H pylori infection and blepharitis?

Glaucoma and Helicobacter pylori infection: correlations and controversies.
Br J Ophthalmol. 2009 Nov;93(11):1420-7.
Izzotti A, Saccà SC, Bagnis A, Recupero SM.
Department of Health Sciences, Faculty of Medicine, University of Genoa, Genoa, Italy.
Comment in:
Br J Ophthalmol. 2009 Nov;93(11):1413-5.

A possible association between Helicobacter pylori infection and eye diseases, including Sjögren syndrome, blepharitis, central serous chorioretinopathy and uveitis, has been proposed. Glaucoma is the second leading cause of blindness in the world, after cataracts, and the leading cause of irreversible blindness, but many aspects of its pathogenesis remain unknown. H pylori infection may influence the pathophysiology of glaucoma by releasing various proinflammatory and vasoactive substances, as well as by influencing the apoptotic process, parameters that may also exert their own effects in the induction and/or progression of glaucomatous neuropathy. It is difficult to understand how H pylori infection can be linked to such varied pathologies. Systemic H pylori-induced oxidative damage may be the mechanism which links oxidative stress, H pylori infection and the damage to the trabecular meshwork and optical nerve head that results in glaucoma.

Wednesday, November 4, 2009

Abstract: How Azasite acts on the ocular surface & lids

Very, very interesting.

Wish this stuff didn't cost more than its weight in gold.

Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation.
J Ocul Pharmacol Ther. 2009 Oct;25(5):433-9.
Akpek EK, Vittitow J, Verhoeven RS, Brubaker K, Amar T, Powell KD, Boyer JL, Crean C.
The Ocular Surface Diseases and Dry Eye Clinic, The Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.

PURPOSE: To investigate the ocular distribution of 1% azithromycin ophthalmic solution and the effect of polycarbophil-based mucoadhesive formulation on ocular tissue levels of azithromycin after single and multiple topical administrations in the rabbit eye.

METHODS: Rabbits were treated with either a single administration of 1% azithromycin solution with or without polycarbophil, or with multiple administrations of 1% azithromycin solution in polycarbophil. Drug concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor, and tear samples were analyzed over a period of 144 h after a single administration of azithromycin with or without polycarbophil. Eyelid, conjunctiva, cornea, aqueous humor, and tear samples were collected over a period of 288 h during and after multiple administrations of azithromycin.

RESULTS: Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific half-lives of 15, 63, and 67 h, respectively. Following multiple administrations, the drug gradually accumulated. The polycarbophil formulation increased the bioavailability of the drug, producing peak concentrations that were between 5- and 12-fold higher than those without polycarbophil. Azithromycin also distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six days after treatment was discontinued, eyelid levels of azithromycin were above 40 microg/g.

CONCLUSIONS: Sustained and high concentrations were encountered with 7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues, particularly the lids. Many ocular surface disorders involving the tear film, eyelids, and adnexal structures are associated with chronic, low-grade bacterial infection and may potentially lead to decreased vision secondary to corneal scarring. Various topical antibiotic and steroid combinations with or without oral tetracyclines are commonly used with variable clinical response and known potential side effects. The clinical relevance of this study is unknown; however, the long-lasting antibacterial and additional anti-inflammatory properties of topical azithromycin might offer an effective alternative treatment option and should be explored further in clinical studies.

Abstract: NAAGA/Naabak eyedrops

Never heard of it. But Dr. Christophe Baudouin is generally thought to be pretty much the world expert on dry eye, so I hope to learn more.

[Evaluation of NAAGA efficacy in dry eye syndrome.]
J Fr Ophtalmol. 2009 Oct 23. [Epub ahead of print]
[Article in French]
Baudouin-Brignole F, Robert PY, Creuzot-Garcher C, Olmiere C, Delval L, Baudouin C.

Centre National d'Ophtalmologie des Quinze-Vingts et UMR_S INSERM 968, Institut de la Vision, Université Paris 6, Paris; Laboratoire de Toxicologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris.

OBJECTIVES: The aim of this study was to assess the efficacy of Naabak(R) eyedrops in reducing inflammation in dry eye syndrome.

PATIENTS AND METHODS: This pilot, multicenter, randomized, double-blind, parallel study was carried out in adult patients suffering from moderate dry eye syndrome. Patients were treated for three months with preservative-free NAAGA (Naabak(R)) or with sodium chloride 0.9% without preservative (Larmabak(R)). They received the treatment four to six times a day during the 1(st) month and three to four times a day during the 2(nd) and 3(rd) months. At each visit (D28 and D84), clinical tests were performed as well as a biological evaluation of HLA-DR and MUC5AC expression on conjunctival imprints using flow cytometry.

RESULTS: After three months of treatment, the ocular surface symptoms and overall discomfort were improved in patients treated with Naabak(R) and in those treated with Larmabak(R) with no significant difference between the groups. Cytological impression showed a significant decrease in the expression of inflammatory markers, notably antigen HLA-DR, in the Naabak(R) group.

CONCLUSION: This study confirms the anti-inflammatory property of preservative-free NAAGA (Naabak(R)) in the context of dry eye syndrome with a similar clinical efficacy compared to sodium chloride solution (Larmabak(R)). Naabak(R) could present an additional advantage compared to artificial tears and could be indicated in the treatment of moderate inflammatory dry eye syndrome.

Abstract: Expression of CXCL9/10/11 + CXCR3 in DES' pt tear film

...Continuing in the perennial hunt for The Dry Eye Diagnostic. Quite interesting actually.

Expression of CXCL9, CXCL10, and CXCL11, and CXCR3 in the Tear Film and Ocular Surface of Patients with Dry Eye Syndrome.
Invest Ophthalmol Vis Sci. 2009 Oct 22. [Epub ahead of print]
Yoon KC, Park CS, You IC, Choi HJ, Lee KH, Im SK, Park HY, Pflugfelder SC.

Purpose: To investigate the expression of CXCL9, CXCL10, CXCL11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome.

Methods: Thirty-three patients with dry eye (16 Sjögren's syndrome and 17 non-Sjögren's syndrome patients) and 15 control subjects were recruited. The concentrations of CXCL9, CXCL10, and CXCL11 in tears were measured using enzyme-linked immunosorbent assay. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. Expression of CXCL9, CXCL10, CXCL11, and CXCR3 in the conjunctiva was evaluated using immunohistochemistry. Flow cytometry was performed to count CXCR3+ cells and CXCR3+CD4+ cells in the conjunctiva.

Results: The concentrations of CXCL9, CXCL10, and CXCL11 were 1,148+/-1,088, 24,338+/-8,706, and 853+/-334 pg/ml in dry eye patients, and 272+/-269 (P=0.01), 18,149+/-5,266 (P=0.02), and 486+/-175 (P<0.01) pg/ml in control subjects, respectively. The concentrations significantly increased in tears of Sjögren's syndrome patients compared with those of non-Sjögren's syndrome patients (P<0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P<0.05). Staining for CXCL9, CXCL10, CXCL11 and CXCR3 increased in dry eye patients, especially in Sjögren's syndrome patients. Flow cytometry demonstrated an increased number of CXCR3+ cells and CXCR3+CD4+ cells in dry eye patients.

Conclusions: Expression of CXCL9, CXCL10, CXCL11, and CXCR3 increases in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlate significantly with various tear film and ocular surface parameters.

Drug updates: ISTA's low-dose bromfenac

In their 3Q 2009 results, ISTA stated they expect their new low-dose bromfenac for dry eye (for which positive Phase II results were announced last spring) to enter Phase III trials in the first half of 2010.

Drug/device news: EGP-437 update

I don't think I've posted about this one before although I have it on the clinical trial roster.

EyeWorld reports from this years AAO the following:

Ionized drug demonstrates rapid onset and long-lasting action in patients with dry eye

SAN FRANCISCO — A topical dexamethasone administration that is delivered to the eye by a novel drug delivery system involving ionization of drug particles by electrical current rapidly decreases clinical signs and symptoms related to dry eye, according to a poster presented here.

In a study, patients who received either a low-dose or high-dose application of EGP-437 (dexamethasone phosphate ophthalmic solution optimized for iontophoresis, EyeGate Pharma and Ora) reported a significant decrease in ocular discomfort after exposure to a controlled adverse environmental (CAE) challenge, which exacerbates dry eye signs and symptoms, compared with placebo, according to a poster presented at the joint meeting of the American Academy of Ophthalmology and Pan-American Association of Ophthalmology.

As well, study drug patients had a significant decrease in inferior region fluorescein staining at their seventh visit compared with baseline, which "demonstrates that two EGP-437 treatments over 3 weeks, which include three CAE visits, may aid healing in this region," according to the poster.

Diagnostics: TearLab trial results

Sounds like they have made some really good progress with this now:

TearLab Presents Results of Landmark Dry Eye Trial at AAO -- PAAO 2009 Joint Meeting

SAN DIEGO, Oct. 26, 2009 (GLOBE NEWSWIRE) -- OccuLogix, Inc. dba TearLab Corporation (Nasdaq:TEAR) (TSX:TLB) announced that Gary Foulks, MD, FACS, presented the poster, "Osmolarity as a Biomarker for Disease Severity in Mild to Moderate Dry Eye Disease," from the TearLab Osmolarity Core Validation Study today at the 2009 American Academy of Ophthalmology (AAO) and Pan American Ophthalmology (PAAO) joint meeting in San Francisco, California.

Dry Eye Disease and a New Severity Index

Data from this landmark study compares the results of individual clinical evaluations to Dry Eye Disease (DED) severity. Over 300 subjects were evaluated in 10 sites worldwide, and for the first time a comprehensive index has been created to classify patients into Normal, Mild/Moderate or Severe categories using an objective and quantitative analysis.

"DED has traditionally been very difficult to diagnose in early and mild stages due to compensatory mechanisms that are in effect during the early transitory phases of the disease. This difficulty to diagnose early stage disease has long been a confounding problem to clinicians and pharmaceutical companies alike. Data from this study clearly demonstrates that in earlier stages of disease, osmolarity shows a progressive increase with increasing severity," stated Dr. Foulks.

Elias Vamvakas, Chairman and Chief Executive Officer of TearLab Corporation, commented, " We are very excited about the results of this study. The demonstrated accuracy and sensitivity of our lab-on-a-chip technology is a breakthrough that will enable doctors to easily diagnose and effectively manage patients with DED. In addition we believe the test will become the catalyst to effective drug development and appropriate prescription."

The TearLab(TM) Osmolarity System

The TearLab(TM) Osmolarity System uses a novel lab-on-a-chip approach that requires less than 50 nL (nanoliters) of tear fluid in order to measure tear osmolarity. The TearLab(TM) Osmolarity System is a breakthrough test that will enable doctors to easily diagnose and effectively manage patients with Dry Eye Disease. The TearLab(TM) Osmolarity System eliminates the challenges that previously prevented point-of-care osmolarity testing. The TearLab(TM) System can produce a sample-to-answer result in less than 30 seconds and is intended to be technician administered.