Thursday, September 10, 2009

Abstract: The double whammy

Restasis plus steroid, for chronic dry eye.

Efficacy of Combined 0.05% Cyclosporine and 1% Methylprednisolone Treatment for Chronic Dry Eye.
Cornea. 2009 Aug 31. [Epub ahead of print]
Byun YJ, Kim TI, Kwon SM, Seo KY, Kim SW, Kim EK, Park WC.
From the *Vision Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea; daggerDepartment of Ophthalmology, Dong-A University College of Medicine, Busan, Korea; and double daggerDepartment of Ophthalmology, Soonchunhayng University College of Medicine, Bucheon, Korea.

PURPOSE:: To compare the efficacy of cyclosporine 0.05% (tCSA) and combined treatment with 1% methylprednisolone on treatment of moderate-to-severe chronic dry eye.

PATIENTS AND METHODS:: Forty-four patients with moderate-to-severe dry eye who had not responded to conventional treatment were treated with tCSA for 3 months. Twenty-one subjects (Group 1) were treated with 1% methyl prednisolone and tCSA for initial 3 weeks, and treated with tCSA only thereafter and 23 subjects (Group 2) were treated with tCSA only. Symptom scores, Tear break-up time (TBUT), Schirmer score, and corneal and conjunctival fluorescein staining were evaluated before and at 1, 2, and 3 months after treatment. Proinflammatory factors, interleukin-6, and interleukin-8 tear concentration were measured before and at 3 months.

RESULTS:: Symptom scores, Schirmer scores, TBUT score, corneal fluorescein, conjunctival staining showed significant improvement at 1 month compared to baseline in group 1 (all P < 0.001), and all the same but few exceptions in group 2 (P = 0.002 on Schirmer, P = 0.267 on cornea stating). In symptom scores, Schirmer scores and corneal staining, greater improvements were observed for group 1 at 1 month compared to group 2 (P < 0.001, P = 0.039, P = 0.01, respectively). However, in TBUT score and conjunctival staining, there were no between-group differences (P = 0.277, P = 0.254, respectively). The time interval from treatment initiation to symptom relief was shorter for group 1 than group 2. Both groups showed decreased tear IL-6 and IL-8 concentrations at 3 months compared to baseline levels (P < 0.05). However, no between-group differences were noted in mean concentrations of IL-6 and IL-8 at baseline and at 3 months.

CONCLUSIONS:: Treatment with tCSA appears to be safe and effective in moderate-to-severe chronic dry eye. Additional short-term use of a topical steroid had the benefit of providing faster symptom relief and improvement of ocular sign without serious complications.

Abstract: Analyzing cytokines in dry eye patients

Analysis of Inflammatory Cytokines in the Tears of Dry Eye Patients.
Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA.
From the Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York.
Cornea. 2009 Aug 29. [Epub ahead of print]
PURPOSE:: To determine the levels of 8 important cytokines and 1 chemokine in tears of patients with dry eye disease.

METHODS:: Tear samples were collected from 7 patients with dry eye disease and 7 healthy volunteers, and impression cytology samples were collected from 3 of the dry eye patients and 3 of the normal controls. Tears were analyzed for the presence of 8 cytokines [interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-1beta] and 1 chemokine (IL-8). The cytokines and chemokine in each tear sample were measured using Invitrogen's Multiplex Bead Immunoassays. The impression cytology samples were analyzed for IL-1beta, IL-6, IL-8, and TNF-alpha mRNA expression using real-time reverse transcriptase polymerase chain reaction anlaysis.

RESULTS:: All cytokines and the chemokine measured were significantly increased in the tears of dry eye patients as compared to normal controls. mRNA of all four markers was increased, and the fold increase correlated well with the fold increase of the cytokine concentration found in the tear samples.

CONCLUSION:: Tears from dry eye patients contain significantly increased concentrations of cytokines that show correlation to severity of the disease. The upregulation of their respective genes in the conjunctiva suggests that the concentration increase is not the result of evaporative effects, but of overproduction. These findings suggest that cytokines may play an important role in dry eye disease and topical cytokine modulators may be explored as a therapeutic approach to dry eye disease.

Abstract: Dry eye and chronic hepatitis C

Evaluation of Ocular Surface Damage and Dry Eye Status in Chronic Hepatitis C at Different Stages of Hepatic Fibrosis.
Cornea. 2009 Aug 29. [Epub ahead of print]
Gumus K, Yurci A, Mirza E, Arda H, Oner A, Topaktas D, Karakucuk S.
From the *Department of Ophthalmology and the daggerDepartment of Internal Medicine, Division of Gastroenterology, Erciyes University School of Medicine, Kayseri, Turkey.

PURPOSE:: The purpose of this study was to explore changes in ocular surface and tear function parameters in chronic hepatitis C at different stages of hepatic fibrosis.

METHODS:: Fifty-four patients with biopsy-proven chronic hepatitis C and 54 age- and sex-matched healthy control subjects without systemic hepatitis C infection were examined with the Ocular Surface Disease Index questionnaire, Schirmer with and without anesthesia, tear film breakup time, and scoring of ocular surface Lissamine green staining using modified Oxford and van Bijsterveld scoring systems and corneal fluorescein staining.

RESULTS:: Patients with chronic hepatitis C scored significantly worse than the control subjects on all parameters: modified Oxford scores of Lissamine green staining (5.5/3.0; P <0.001), Oxford and van Bijsterveld scores (4.0/2.0; P <0.001), and corneal fluorescein staining (1.5/0.0; P = 0.001). The chronic hepatitis C group also had higher Ocular Surface Disease Index scores than the control subjects (22.3/13.7; P = 0.001). Schirmer with and without anesthesia and tear film breakup time scores were found to be lower in patients with chronic hepatitis C (P <0.001). Moreover, patients with advanced stages of hepatic fibrosis (stages 4-6) had significantly lower values of tear film breakup time and worse Ocular Surface Disease Index scores and ocular surface vital dye staining than those with initial stages of hepatic fibrosis (stages 0-3).

CONCLUSION:: Patients with chronic hepatitis C, especially those with advanced stages of hepatic fibrosis, were more likely to exhibit severe ocular surface damage and signs of dry eye.

Abstract: Measuring pachymetry of tear film

A Novel Method for Pachymetry Mapping of Human Precorneal Tear Film Using Pentacam with Fluorescein.
Invest Ophthalmol Vis Sci. 2009 Aug 26. [Epub ahead of print]
Zhuang H, Zhou XT, Xu J.
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Purpose. To report a novel method for pachymetry mapping of human precorneal tear film using Pentacam.

Methods. Precorneal tear film is undetected by Pentacam routinely but that could be well visualized with aid of fluorescein. Twenty dry eye patients and twenty age-matched normal subjects were enrolled in this prospective study. Right eye of each subject was scanned once with Pentacam and rescanned after instillation of 1 microl 0.1% fluorescein. And the differential map of corneal thickness between two measurements is identified as the pachymetry map of tear film. Then central tear film thickness was evaluated and pattern of each pachymetry map was determined.

Results. The mean central tear film thickness in dry eyes 22.2 +/- 4.5 microm was less than in normal eyes 24.7 +/- 3.9 microm (student's t test, P = 0.0614). Additionally, tear film pachymetry map could be classified into three patterns: Pattern 1 "thickening upwards", Pattern 2 "uniform distribution", and Pattern 3 "thickening downwards". Tear film pachymetry maps of normal eyes consist of Pattern 1 (40%), Pattern 2 (40%) and Pattern 3 (20%), while those of dry eyes consist of Pattern 1 (70%), Pattern 2 (20%) and Pattern 3 (10%). Dry eyes tended to have a higher proportion of Pattern 1 pachymetry maps than normal eyes, although still no significant difference was found between two groups (CMH chi2 test, P = 0.0852).

Conclusions. The novel method feasibly could be used to map the tear film thicknss which provides a valuable means to investigate the spatial distribution of tear film.

Abstract: Don't forget demodex in the bleph diagnosis....

[Ectoparasites. Part 2: Bed bugs, Demodex, sand fleas and cutaneous larva migrans]
[Article in German]
Hautarzt. 2009 Sep;60(9):749-57; quiz 758-9.
Nenoff P, Handrick W, Krüger C, Herrmann J, Schmoranzer B, Paasch U.
Haut- und Laborarzt/Allergologie, Andrologie, Laboratorium für medizinische Mikrobiologie, Strasse des Friedens 8, 04579, Mölbis.
Ectoparasites or epidermal parasites include a very heterogenous group of infections of the outer layers of the skin. Worldwide the most common are scabies, lice, tungiasis, and hookworm-induced cutaneous larva migrans. In recent years, bed bug infestations in hotels or vacation homes seem to have become more frequent. Demodex folliculorum and Demodex brevis are found in the facial and scalp hair follicles in 95% of individuals. Classic Demodex folliculitis is often overlooked in differential diagnostic considerations. This inflammatory sebaceous gland disease as well as Demodex blepharitis both provide a diagnostic and therapeutic challenge. Permethrin can be used topically against demodicosis. Vacationers who go barefoot on beaches in tropical Africa, South America and subtropical Asia risk infestations from female sand fleas. The lesions can be curetted or removed with a punch biopsy, then treated with antiseptics or even systemic antibiotics if a secondary infection develops. Cutaneous larva migrans is one of the most common imported ectoparasite infections from the tropics. Topical treatment measures include thiabendazole or cryotherapy. If the infestation is severe, systemic antihelminthics or ivermectin can be employed.

Drug news: Preservative free glaucoma med in UK

First preservative-free ophthalmic prostaglandin for glaucoma now available in the UK
Pharmiweb, Sept 3 2009

Hoddesdon, 3rd September 2009 — ‘Saflutan’TM?(tafluprost), the first preservative-free ophthalmic prostaglandin in the UK, is now available for the reduction of elevated intraocular pressure (IOP) in the most common type of glaucoma (open angle glaucoma) and in ocular hypertension. Treatment with tafluprost has been shown to provide sustained IOP control with a clinical study showing a 33% mean reduction in IOP. Unlike tafluprost, all other prostaglandins currently available for glaucoma contain a preservative that can cause adverse reactions in some patients including burning, itching, tearing or dry-eye sensation.

According to a multinational Phase III study involving 533 patients, tafluprost provided significant reductions in IOP (7.0mmHg at 24 months)....

David Wright, Chief Executive of the International Glaucoma Association commented: "The prostaglandin and prostamide analogue eye drops used for the control of intraocular pressure (IOP) in glaucoma represent the greatest advance in glaucoma treatment of recent years. The introduction of Saflutan is a particularly welcome addition to the range of these most powerful medications because its preservative-free formulation will allow those patients who are allergic to preservatives to benefit from the control of IOP offered by this class of medication that was hitherto unavailable".

Abstract: Topical tranilast in GVHD dry eye

Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD.
Bone Marrow Transplant. 2009 Jul 27. [Epub ahead of print]
Ogawa Y, Dogru M, Uchino M, Tatematsu Y, Kamoi M, Yamamoto Y, Ogawa J, Ishida R, Kaido M, Hara S, Matsumoto Y, Kawakita T, Okamoto S, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Fibrosis and excessive extracellular matrix production are characteristic features of lacrimal gland chronic GVHD (cGVHD). Tranilast (n-[3,4-anthoranilic acid]), used for fibrotic skin disease, inhibits transforming growth factor-beta-induced matrix production. We conducted a non-randomized study comparing 8 patients (five men, three women; median age, 47 years) given topical tranilast with 10 patients (three men, seven women; median age, 37 years) receiving therapy with topical artificial tears, sodium hyaluronate and vitamin A for mild ocular cGVHD. The tranilast group instilled topical tranilast and artificial tears q.i.d., beginning the day of dry eye diagnosis. The ocular surface and tear dynamics of each patient were evaluated before hematopoietic stem cell transplant, at the onset of dry eye and after 3 months of treatment. At 3 months, the scores of the Rose Bengal test and Schirmer test with nasal stimulation had significantly improved in the tranilast group compared with that in the control group (P<0.05). Furthermore, although five control patients (50%) developed severe dry eye within the treatment period, only one tranilast-treated patient (12.5%) did; the rest still had mild dry eye (P<0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD.Bone Marrow Transplantation advance online publication, 27 July 2009; doi:10.1038/bmt.2009.173.

Abstract: NGF and contact lens wear

Great to see more contact lens/dry eye research going on.

Elevated nerve growth factor in dry eye associated with established contact lens wear.
Eye Contact Lens. 2009 Sep;35(5):232-7.
Liu Q, McDermott AM, Miller WL.

College of Optometry, University of Houston, Houston, TX 77204-2020, USA.
PURPOSE: Nerve growth factor (NGF) has been shown to be upregulated in conditions, which damage corneal nerves and to relieve dry eye. How NGF changes in nerve injury induced by established contact lens wear is not clear. The purpose of this study was to measure the subepithelial nerve plexus and tear NGF and transforming growth factor (TGF)-beta1 levels in patients with established contact lens associated with dry eye.

METHODS: Non-contact lens wearers and subjects who had worn soft contact lenses for more than 1 year were recruited and were divided into three groups: (1) normal controls; (2) contact lens wearers without dry eye; (3) contact lens wearers with dry eye. Corneal sensitivity was measured with a Cochet-Bonnet aesthesiometer. Nerve density and branching in the subepithelial plexus were measured using in vivo confocal microscopy. Tear NGF and TGF-beta1 levels were measured with an enzyme immuno assay.

RESULTS: There was a statistically significant decrease of corneal sensitivity in contact lens wearers compared with normal controls. The nerve density in the subepithelial plexus of contact lens wearers with dry eye was 538.8 +/- 39.3 microm/image (3.959 +/- 0.28 pm/microm(2)) and 537.1 +/- 30.9 microm/image (3.947 +/- 0.27 pm/microm(2)) in those without dry eye. Both of these values were significantly (P=0.032) lower than in the normal controls (4.412 +/- 0.21 pm/microm(2)). The concentration of tear NGF was increased in contact lens wearers with dry eye and was statistically significantly greater compared with contact lens wearers without dry eye. Transforming growth factor-beta1 levels were found to increase one fold in contact lens associated dry eye, and were significantly correlated to NGF.

CONCLUSIONS: Corneal subepithelial nerve density was decreased in long-term contact lens wear but this change was not significantly correlated with tear film NGF concentration. Tear film NGF levels were elevated in contact lens related dry eye, likely in response to anti-inflammatory factors such as TGF-beta1.

Abstract: Dry eye in sealed buildings.

Symptoms prevalence among office workers of a sealed versus a non-sealed building: Associations to indoor air quality.
Environ Int. 2009 Aug 7. [Epub ahead of print]
Rios JL, Boechat JL, Gioda A, Santos CY, Aquino Neto FR, Lapa E Silva JR.
Federal University of Rio de Janeiro, Brazil. Clementino Fraga Filho University Hospital, Institute of Thoracic Diseases.
OBJECTIVES: An increasing number of complaints related to time spent in artificially ventilated buildings have been progressively reported and attributed, at least in part, to physical and chemical exposures in the office environment. The objective of this research was to investigate the association between the prevalence of work-related symptoms and the indoor air quality, comparing a sealed office building with a naturally ventilated one, considering, specially, the indoor concentration of TPM, TVOCs and the main individual VOCs.

METHODS: A cross-sectional study was performed to compare the prevalence of sick building syndrome (SBS) symptoms among 1736 office workers of a sealed office building and 950 of a non-sealed one, both in Rio de Janeiro's downtown. The prevalence of symptoms was obtained by a SBS standardized questionnaire. The IAQ of the buildings was evaluated through specific methods, to determine the temperature, humidity, particulate matter and volatile organic compound (VOC) concentrations.

RESULTS: Upper airways and ophthalmic symptoms, tiredness and headache were highly prevalent in both buildings. Some symptoms were more prevalent in the sealed building: "eye dryness" 33.3% and 27.1% (p: 0.01); "runny nose" 37.3% and 31.3% (p: 0.03); "dry throat" 42% and 36% (p: 0.02); and "lethargy" 58.5% and 50.5% (p: 0.03) respectively. However, relative humidity and indoor total particulate matter (TPM) concentration as well as total volatile organic compounds (TVOCs) were paradoxically greater in the non-sealed building, in which aromatic compounds had higher concentration, especially benzene. The analysis between measured exposure levels and resulting symptoms showed no association among its prevalence and TPM, TVOCs, benzene or toluene concentration in none of the buildings.

CONCLUSIONS: Other disregarded factors, like undetected VOCs, mites, molds and endotoxin concentrations, may be associated to the greater prevalence of symptoms in the sealed building.

Abstract: Predicting dry eye in new contact lens wearers

The cynic in me (which incidentally seems to be working overtime this morning while catching up on medline) is leaping ahead to anticipate what doctors might do with results like these. Put all patients who fit the risk parameters on Restasis before they start wearing contacts, to maximize their early success in contacts? (Down, boy, down.)

A novel method to predict the dry eye symptoms in new contact lens wearers.
Optom Vis Sci. 2009 Sep;86(9):E1042-50.
Pult H, Murphy PJ, Purslow C.
School of Optometry and Vision Sciences, Contact Lens and Anterior Eye Research (CLAER) Unit, Cardiff University, Wales, United Kingdom.
PURPOSE: Lid wiper epitheliopathy (LWE) and lid parallel conjunctival folds (LIPCOF) give moderate prediction levels for dryness symptoms in experienced contact lens (CL) wearers. This study investigated whether a combination of LWE and LIPCOF plus other tear film tests and subjective evaluation before contact lens fitting was better able to predict CL-induced dry eye (CLIDE) symptoms.

METHODS: Tear meniscus height, non-invasive break-up time (NIBUT), ocular hyperaemia, LIPCOF, phenol red thread test, corneal and conjunctival staining, and LWE of the right eye of 33 new soft CL wearers (12 males, 21 females, median age = 30.5 years; range = 19 to 44) were assessed in a prospective 2-mo longitudinal study. Symptoms were evaluated by the Ocular Surface Disease Index (OSDI) and subjects were grouped according to their response in the Contact Lens Dry Eye Questionnaire (CLDEQ) during the study (20 symptomatic and 13 asymptomatic). The subjects were fitted with vifilcon A and senofilcon A lenses for a 2-week period, consecutively.

RESULTS: Limbal hyperaemia (repeated measures analysis of variance; p < 0.05) and LWE (Friedman; p < 0.004) increased significantly during the study but not LIPCOF (p > or = 0.318; temporal, nasal, and Sum), bulbar hyperaemia (p = 0.432), staining (p > or = 0.060), OSDI (p = 0.126), or CLDEQ (p = 0.317, kappa = 0.279). Limbal hyperaemia significantly decreased in senofilcon A lenses. Wearing comfort among symptomatics was significantly better with senofilcon A (p = 0.005). At the enrolment visit, the subjects who became symptomatic exhibited significantly decreased NIBUT and increased LIPCOF and OSDI (range, p < 0.027). The best test combination to predict CLIDE (logistic regression analyses) was LIPCOF Sum plus NIBUT and OSDI, (positive predictive value = 87% and accuracy = 91%).

CONCLUSIONS: LIPCOF, NIBUT, and OSDI are significant discriminators for CLIDE in new CL wearers compared with hyperaemia, tear meniscus height, phenol red thread test, staining, and LWE. The best test combination is NIBUT plus LIPCOF Sum and OSDI (named the Contact-Lens-Predicting-Test).

Abstract: Cyclosporine A in review

Treatment of chronic dry eye: focus on cyclosporine.
Clin Ophthalmol. 2008 Dec;2(4):829-36.
Kymionis GD, Bouzoukis DI, Diakonis VF, Siganos C.
Department of Ophthalmology, Vardinoyannion Eye Institute of Crete, University of Crete, Greece.
To review the current treatment of chronic dry eye syndrome, focusing on cyclosporine A (CsA), a systematic literature search was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the use of CsA in dry eye. A manual literature search was also undertaken based on citations in the published articles. The knowledge on the pathogenesis of dry eye syndrome has changed dramatically during the last few years. Inflammation and the interruption of the inflammatory cascade seem to be the main focus of the ophthalmologic community in the treatment of dry eye, giving the anti-inflammatory therapy a new critical role. The infiltration of T-cells in the conjuctiva tissue and the presence of cytokines and proteasis in the tear fluid were the main reason introducing the use of immunomodulator agents such as corticosteroids, cyclosporine, and doxycicline in order to treat dry eye syndrome. CsA emulsion is approved by the FDA for the treatment of dry eye, while clinical trials of this agent have demonstrated efficacy and safety of CsA. CsA seems to be a promising treatment against dry eye disease. New agents focused on the inflammatory pathogenesis of this syndrome in combination with CsA may be the future in the quest of treating dry eye. More studies are needed to determine the efficacy, safety, timing, and relative cost/effect of CsA.

Abstract: Systane after LASIK

I hate to tell you this, Dan, but according to Steve's recent research, post lasik dry eye at 1 month doesn't really happen anyway, so this study might have been a waste of time. On second thought... maybe all his patients used Systane, or maybe your placebo patients in this study were freaks of nature.

A randomized clinical evaluation of the safety of Systane Lubricant Eye Drops for the relief of dry eye symptoms following LASIK refractive surgery.
Clin Ophthalmol. 2008 Dec;2(4):973-9.
Durrie D, Stahl J.
Durrie Vision, Overland Park, Kansas, USA.
PURPOSE: To evaluate the safety of Systane((R)) Lubricant Eye Drops in relieving the symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK) surgery.

METHODS: This was a randomized, double-masked, single-center, placebo-controlled, contralateral eye study of 30 patients undergoing LASIK surgery. The mean age of patients was 42.4 +/- 10.7 years, and the mean spherical equivalent was -3.29 (range, +1.75 to -7.38). Patients' right and left eyes were randomized to receive either Systane((R)) or placebo - a preserved, thimerosal-free saline solution - beginning from the day of surgery and ending 30 days following surgery. Outcome measures included tear film break up time (TFBUT), visual acuity, degree of corneal and conjunctival staining, and treatment-related adverse events.

RESULTS: Preoperatively, placebo-treated eyes had statistically significantly higher sum corneal staining score than Systane((R))-treated eyes (p = 0.0464); however, the difference was clinically insignificant (p = 0.27). Two weeks post operatively, the average TFBUT in the Systane((R))-treated eyes was 1.23 seconds longer than that of the placebo-treated eyes (p = 0.028). All other evaluated variables were comparable between the two treatments. No adverse events were reported in the study.

CONCLUSION: Systane((R)) Lubricant Eye Drops are safe for use following LASIK surgery to relieve the discomfort symptoms of dry eye associated with the procedure.

Abstract: Optive

Gee, earthshattering. Yes, people feel better with artificial tears and usually feel better when they switch to a slightly better one than they were using, at least for awhile.

Treatment of patients with keratoconjunctivitis sicca with Optive: results of a multicenter, open-label observational study in Germany.
Kaercher T, Buchholz P, Kimmich F.
Clin Ophthalmol. 2009;3:33-9. Epub 2009 Jun 2.
Augenarztpraxis, Heidelberg, Germany;
OBJECTIVE: To evaluate the efficacy and tolerability of Optive, a new dry eye product containing sodium carboxymethylcellulose (0.5%) and glycerol (0.9%), in patients with keratoconjunctivitis sicca (KCS).

METHODS: This was a non-interventional and observational study including patients with dry eye who required a change of medication or were naïve to dry eye treatment (N = 5,277). Disease severity, tear break-up time (TBUT), tolerability, and change in clinical symptoms were recorded at baseline and at final visit (2 to 4 weeks after first treatment).

RESULTS: The severity of KCS was mild in 18.6%, moderate in 59.9%, and severe in 21.5% of patients based on physicians' assessment. TBUT was measured in 4,338 patients before switching to or initiating therapy with Optive and at final visit. Baseline measurement of mean TBUT was 7.7 +/- 3.9 seconds. This value increased to 10.0 +/- 4.7 seconds at final visit. Most patients (85.4%) reported improvement in local comfort. The majority (75.1%) of patients felt an improvement in symptoms after changing their treatment. Two percent of patients reported adverse events, and 0.4% were treatment-related.

CONCLUSIONS: Optive was well tolerated and improved the symptoms of dry eye after 2 to 4 weeks.

Abstract: Literature survey - inflammation, antiinflammatory therapies in dry eye

The role of inflammation and antiinflammation therapies in keratoconjunctivitis sicca.
Clin Ophthalmol. 2009;3:57-67. Epub 2009 Jun 2.
Gumus K, Cavanagh DH.
Department of Ophthalmology, Erciyes University School of Medicine, Kayseri, Turkey;
PURPOSE: To review and integrate recent advances in identifying the role of inflammation in the pathogenesis of dry eye conditions and the biological rationale and practical clinical aspects of newer, antiinflammatory theories.

METHODS: A comprehensive literature survey.

RESULTS AND CONCLUSION: Keratoconjunctivitis Sicca (KCS) is a multifactorial and complex disorder in which ocular surface inflammations play a central role. Identification of specific CD4-T-Cell pathways and the recent recognition of targeting of alpha-fodrin suggest a case for novel new therapeutic aspects such as anti-CD4 monoclonal antibodies, systemic linoleic and gamma-linolenic acids, and omega-6 essential fatty acids. Replacement of tear volume with nonpreserved wetting agents and standard typical antiinflammatory corticosteroid and/or cyclosporine A continues to be central current conventional therapy for KCS.

Abstract: Dry eye in juvenile arthritis

An evaluation of dry eye symptoms and signs in a cohort of children with juvenile idiopathic arthritis.
Clin Ophthalmol. 2009;3:271-5. Epub 2009 Jun 2.
Kotaniemi KM, Salomaa PM, Sihto-Kauppi K, Säilä HM, Kauppi MJ.
Department of Ophthalmology;
OBJECTIVE: To determine the prevalence of dry eye symptoms and signs in children with juvenile idiopathic arthritis (JIA). P

ATIENTS AND METHODS: A total of 192 children with JIA: 48 oligo-, 39 extended oligo-, 79 polyarthritis, and 26 with other types of arthritis (eight juvenile spondyloarthritis, five juvenile psoriatic arthritis, three mixed connective tissue diseases, two systemic onset arthritis, and eight undetermined arthritis) were interviewed for dry eye symptoms and tested with Schirmer test with anesthetic. Two thirds of the patients were female and the mean age of the patients was 13.1 years (range 10-16) and the mean duration of arthritis was six years (SD 4, 4). Thirty-one percent of the patients had a history of uveitis. Dry eye was defined as Schirmer test score < /= 5 mm in five minutes. The type of arthritis, a history of uveitis, and the ocular and systemic medication used were evaluated for their correlation with dry eye symptoms and signs by using chi-square tests and the Mann-Whitney Monte Carlo analysis.

RESULTS: Altogether 17% of this cohort had decreased basal tear secretion. The most common symptoms of dry eye were discharge secretion, itching, and watering. The intensity of symptoms and signs did not correlate. The type of arthritis, a history or presence of uveitis, and the medication used did not correlate with the occurrence of dry eyes.

CONCLUSION: Dry eye symptoms and signs are common in JIA, and Schirmer test with anesthetic is a useful tool in evaluating these patients.

Abstract: The meibomian puzzle

Well, it's a puzzle alright. And for those of you who have often wondered, "Geez, with all of modern medical technology why can't they come up with a decent tear substitute?" perhaps this article will help explain why - bearing in mind of course that this is discussing meibum which is only a very small albeit critical part of the tear film.

I found the summary of this 'state-of-the-meibomian-knowledge-nation' review fascinating and those of you who are really into MGs may want to get a copy of the complete study. The phospholipid point (vs. long chain fatty acids, see my highlight below) was surprising to me and ought to have interesting implications for treatment research.

The Meibomian Puzzle: Combining pieces together.
Prog Retin Eye Res. 2009 Aug 4. [Epub ahead of print]
Butovich IA.
Department of Ophthalmology and Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9057, USA.
The purpose of this review was to summarize the available information on lipidomic analysis of human meibum and tear film, and critically evaluate the pertinent past and present analytical procedures and results obtained in various laboratories. Human meibum was shown to be a very complex mixture of lipids of various classes. For decades, their exact structures have remained elusive. Because of the limitations of the then-current techniques, most of the complex lipids that constitute meibum could not be analyzed as whole molecules and required prior hydrolysis and/or transesterification of the entire lipid pool. These procedures effectively made it very difficult, and often impossible, to reconstruct the complete structures of the original intact compounds, which prompted us to call this The Meibomian Puzzle. Modern techniques such as high-performance liquid chromatography in combination with mass spectrometry help in solving this puzzle by allowing a researcher to detect and analyze intact molecules of complex lipid compounds, even if present in extremely low concentrations. This current de-facto standard procedure in lipidomic analysis of natural lipids and their mixtures is compared with other experimental techniques such as nuclear magnetic resonance spectroscopy, infrared spectroscopy, gas chromatography, and thin layer chromatography, among the others. The results obtained by older techniques, and their limitations and deficiencies are discussed. It appears that some of the earlier findings did not withstand a scrupulous re-evaluation and need to be modified and/or corrected. The most intriguing development is the virtual absence in meibum of typical phospholipids - an important group of amphiphilic compounds whose role in the human tear film was thought to be to stabilize the entire tear film structure. Instead, another group of previously unidentified compounds, very long chain (O-acyl)-omega-hydroxy fatty acids, appears to be a stabilizing factor which might be related to tear film stability and deterioration. Thus, these compounds may become an important target in biochemistry and (patho)physiology of ocular surface and dry eye research.

Abstract: Oral uridine and dry eye

I wasn't familiar with this drug but after googling it... I'd really like to know what dosage was used for this study. (Most of the hits are for psychiatric uses of the drug.)

Preliminary effects of oral uridine on the ocular surface in dry eye patients.
J Korean Med Sci. 2009 Aug;24(4):701-7. Epub 2009 Jul 30.
Chang KC, Oh JY, In YS, Kim MK, Shin KC, Wee WR, Lee JH, Park MG.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.

We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.

Breakthrough medical device (sort of)

I was pleasantly surprised to find that this article was not talking about a medical device per se... but rather a humble flax baggie, much like my favorite rice baggy. Quite right that this concept should be employed routinely by eye doctors. I only wish it was able to keep each and every case of MGD under control, but sadly there are many whose condition does not respond to heat or other usual treatments. article in the UK press:

Simple Device Could Save NHS Millions
ALIFAX, England, August 17 /PRNewswire/ -- A simple eye treatment device developed three years ago by Yorkshire based consultant ophthalmologist, Teifi James was borne out of his 20 years of conducting eye clinics and seeing patients suffering with some aspect of meibomian gland dysfunction (MGD) such as dry eye syndromes, blepharitis, stye and chalazion.

The device marketed as an EyeBag is made from suedex and silk cloth and filled with flax (linseed) and works on the principle of a warm eye compress. Flax seeds are used because of their size and density allowing the EyeBag, once warmed in the microwave, to sit effectively and comfortably across the eyes.

Some 30% of patients referred to ophthalmology/optometry clinics in the UK have some form of MGD with thousands more people experiencing the symptoms of MGD going undiagnosed or untreated.

Drug news: MarketScope's review of dry eye drugs in clinical trials

The August 12 issue of Dave Harmon's MarketScopes Ophthalmic Market Perspectives has a listing of dry eye products in FDA approval process as follows:

Alcon/Lantibio's VISMED (HA drop)- turned down by FDA in June, recommended additional Phase III trial. VisMed is on the market in Europe.

Alcon's VEXOL (non steroidal anti-inflammatory) - completed Phase II trial

ArGentis' ARG101/102 (testosterone topical cream) - completed Phase II trial

Inspire's PROLACRIA (secretagogue) - in Phase III (again)

Lantibio's MOLI1901 (secretagogue) - in Phase III

Sirion's ST609 (cyclosporine 0.1%) - in Phase III

Novagali's CYCLOKAT (cyclosporine with cationic emulsion) - completed Phase II trial

Novagali's CATIONORM (lubricating emulsion) - in Phase III

Ista's XIBROM (low dose steroid) - Phase IIB trial completed

Ista's Ecabet Sodium (secretagogue) - Phase II trial completed

EyeGate's EGP-437 (iontophoresis with dexamethasone) - Phase II trial completed

Otsuka/Acucela's Rebamipide (secretagogue) - in Phase III

Device news: Progress with drug-dispensing contact lens

August 4, Reuters
Drug-dispensing contact lens passes early tests

NEW YORK (Reuters Health) - A contact lens that gradually dispenses a steady stream of medication to the eye could ease treatment for glaucoma and other eye ailments if it advances through animal and human testing, according to new research....

Laboratory tests show that the drug-dispensing contact lens "can release really large amounts of drug for very long periods of time at a very steady rate," Dr. Daniel Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Children's Hospital Boston, noted in a telephone interview with Reuters Health....

Although other groups have developed drug-releasing contact lenses, none have been able to achieve a constant, steady stream of medication at high enough levels to be therapeutic, the researchers note in the journal Investigative Ophthalmology and Visual Science. Prior contact lenses "have released very small amounts of drug for long periods of time or a lot of drug for not a long time," Kohane said.

In the lab tests, contact lens Kohane's team developed dispensed appropriate levels of ciprofloxacin -- an antibiotic used in eye drops -- for 30 days and in some tests for as long as 100 days. "We're talking really large levels of the drug, for example, enough antibiotic to still be effective for that long," Kohane said.

The drug-dispensing contact lenses are the size and thickness of commercially available contact lenses. The researchers have begun testing them in animals and hope to begin human testing soon.

Drug-dispensing contact lenses "could be used with almost any drug that could be applied to the eye, particularly the front of the eye, and for a range of conditions such as glaucoma, allergic conjunctivitis, dry eye, infections, pain, and things like that," Kohane noted.

Abstract: Artificial tears & vision

Contrast sensitivity and tear layer aberrometry in dry eye patients.
Optom Vis Sci. 2009 Sep;86(9):E1059-68.
Ridder WH 3rd, LaMotte J, Hall JQ Jr, Sinn R, Nguyen AL, Abufarie L.

PURPOSE: Dry eye disease is a common condition that affects millions of people world wide. The common findings of dry eye disease are blurred vision and tear film instability. The purpose of this study was to determine if long-term use of artificial tears altered visual disturbances and tear film instability of dry eye patients.

METHODS: Contrast sensitivity and optical aberrations were measured in 22 dry eye and 10 normal patients before and after daily use of artificial tears. The contrast sensitivity and optical aberrations were measured in response to the administration of a single drop of artificial tear placed in the eye.

RESULTS: The short-term effect (i.e., a few minutes) of a single drop of artificial tear placed in the eye was a decrease in contrast sensitivity and an increase in optical aberrations. Long-term daily use of the artificial tears (i.e., up to 2 weeks) resulted in less of a short-term effect in dry eye patients. No long-term effect was observed for normal subjects. Both contrast sensitivity loss and optical aberrations decreased by 35% per week of artificial tear use for the dry eye patients suggesting that the changes in contrast sensitivity were the result of optical aberrations.

CONCLUSIONS: The results suggest that the changes in contrast sensitivity with artificial tear administration were the result of optical aberrations. It appears that long-term use of artificial tears may normalize the tear layer of dry eye disease patients.

Abstract: Dry eye and chlamydia pneumoniae infection

Inconclusive study trying to correlate the two.

[Chlamydia pneumoniae in the etiology of the keratoconjunctivitis sicca in adult patients (a pilot study)]

[Article in Czech]
Cesk Slov Oftalmol. 2009 May;65(3):102-6.
Krásný J, Hrubá D, Netuková M, Kodat V, Tomásová BJ.
Ocní klinika FN Královské Vinohrady, Praha.

AIM: In the pilot study the authors refer to the possible connection between the appearance of keratoconjunctivitis sicca (KCS) and Chlamydia pneumoniae (CP) infection.

MATERIALS AND METHODS: At the Department of Ophthalmology, 10 adult patients older than 45 years were followed up during the period of 5.5-7 years, where in the chronic folicular conjunctivitis caused by CP, the KCS was revealed as the same time.

METHODS: The chlamydial infection diagnosis was established due to the positivity to the familiar (anti-LPS) and species (anti-CP) immunoglobulins (IgG, IgM, and IgA) and to the conjunctival impression specimen, using the indirect immunofluorescence of specific monoclonal antibodies. The patients were treated by means of systemically administered macrolide antibiotics Azithromycine. After the termination of the treatment, the signs of the clinical inflammation of the conjunctival inflammation subsided but the KCS problems remained. After 6 years, the control examinations of the familiar and species antibodies of the CP were performed and the clinical findings of the KCS and its treatment were evaluated.

RESULTS: The decrease of the antibody levels was proved and objective findings and subjective symptoms of KCS in all patients subsided. Altogether 7 patients were without clinical signs of the KCS and without regular application of local artificial tears treatment. At the same time, in two thirds of the patients, the levels of the antibodies decreased or remained unchanged. In the last three patients, the signs of the dry eye decreased, but they didn't disappeared permanently. These patients had to apply artificial tears several times a day. The suspect signs of this serologically active infection persisted despite the antibodies levels' decrease.

CONCLUSION: This pilot study until now didn't confirm the direct dependence between the KCS and CP, but it didn't exclude it as well.

Drug news: Prolacria update

According to their Q2 earnings call, they expect the latest clinical trial to be fully enrolled in the fall. Slow progress towards the goal....

Drug news: Albumin & RU-10

Currently on hold but hopefully not dead.

Dry eye is targeted for development of the drug that contains gene recombination human serum albumin as an effective ingredient. Though the clinical study is currently interrupted, we intend to look for overseas affiliation soon because the need for treatment of dry eye is globally unmet (that is, there are currently few therapeutic drugs).

PRNewsire, July 31

Abstract: Levofloxacin for bleph

A prospective study determining the efficacy of topical 0.5% levofloxacin on bacterial flora of patients with chronic blepharoconjunctivitis.
Graefes Arch Clin Exp Ophthalmol. 2009 Jul;247(7):993-8. Epub 2009 Feb 11.
Yactayo-Miranda Y, Ta CN, He L, Kreutzer TC, Nentwich MM, Kampik A, Mino de Kaspar H.
Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany.
BACKGROUND: To determine the efficacy of conjunctival bacterial eradication following a 1-day, 3-day and 7-day application of topical 0.5% levofloxacin, with and without eyelid scrub, in patients with chronic blepharoconjunctivitis (CBC).

METHODS: Patients with CBC (n = 60) were prospectively randomized to three groups (n = 20 in each group): no antibiotic treatment, topical levofloxacin four times per day in both eyes, and eyelid scrub in addition to topical levovofloxacin four times a day in both eyes. Patients without CBC (n = 40) were enrolled as the negative control group. Cultures of the conjunctiva were obtained from both eyes at baseline, 1 day, 3 days, and 7 days following treatment.

RESULTS: The most common bacteria isolated for all groups at baseline were coagulase-negative Staphylococcus. Eight patients did not complete the study. The remaining 52 patients with CBC had a significantly higher rate of positive thioglycolate broth cultures (94%) compared to a 58% positive culture rate in patient without CBC (P < 0.0001). Treatment with at least 3 days of topical antibiotic in patient with CBC resulted in a significant reduction (P < 0.05) in the number of thioglycolate positive cultures (or= 88%). Following a minimum of a 1-day application of antibiotic, the median colony-forming unit was 0-1 compared to 3-8 for eyes without antibiotic treatment (P < 0.05). Scrubbing of the eyelids did not provide further benefit compared to antibiotic treatment alone.

CONCLUSIONS: CBC eyes have a significantly higher number of positive cultures than eyes without CBC. The application of topical 0.5% levofloxacin for at least 3 days provided a significant reduction in the number of positive cultures as well as the number of bacteria harbored on the conjunctival surface.

Abstract: Confocal microscopy in Sjogrens syndrome

Conjunctival in vivo Confocal Scanning Laser Microscopy in Patients with Sjogren Syndrome (SS).
Invest Ophthalmol Vis Sci. 2009 Aug 20. [Epub ahead of print]
Wakamatsu TH, Sato EA, Matsumoto Y, Ibrahim OM, Dogru M, Kaido M, Ishida R, Tsubota K.
Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Purpose: To demonstrate the conjunctival alterations in patients with Sjögren's (SSDE) and non-Sjögren's syndrome dry eyes (NSSDE) using the HRTII/ RCM confocal microscope, in a prospective controlled study.

Methods: Twenty-eight right eyes from 28 SSDE patients (28 females; mean age: 58.2 +/- 14.3 years), seven right eyes from NSSDE patients (7 females; mean age: 66.1 +/- 14.4 years) and fourteen right eyes of 14 age and sex matched controls were studied. All subjects underwent Schirmer test, tear film break-up time (BUT), vital stainings and confocal microscopy of the temporal bulbar conjunctiva. The density of conjunctival epithelial cells, epithelial microcysts, conjunctival and corneal inflammatory infiltrates were also assessed.

Results: The tear quantity, stability and vital staining scores were significantly worse in patients with SSDE and NSSDE compared to control subjects (p<0.001 and p<0.05, respectively). Eyes of SSDE and NSSDE patients had a significantly higher density of conjunctival and corneal inflammatory infiltrates compared to eyes of controls (p<0.001). Conjunctival inflammatory cell densities showed a negative correlation with tear stability and tear quantity and a positive correlation with the vital staining scores. Conjunctival epithelial cell densities were significantly lower in SSDE and NSSDE compared with control subjects (p<0.05). The density of epithelial cysts was significantly higher in SS compared to healthy controls (p<0.001).

Conclusions: Confocal scanning laser microscopy was an efficient and a noninvasive tool for the quantitative assessment of the conjunctival inflammation and epithelial cell densities as well as evaluation of conjunctival morphological alterations such as microcysts in patients with SSDE and NSSDE dry eye disease.

Abstract: Sex steroids and lacrimal, meibomian glands

David Sullivan & team as usual at the vanguard of hormone research on dry eye. Will be interested to see the next step in this one.

Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?

Mol Vis. 2009 Aug 10;15:1553-72.
Sullivan DA, Jensen RV, Suzuki T, Richards SM.
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.

PURPOSE: We hypothesize that sex steroids induce sex-specific and/or opposite effects in the lacrimal and meibomian glands and that these actions may influence the prevalence of dry eye syndrome. The objective of this study was to begin to test this hypothesis.

METHODS: Lacrimal and meibomian glands were obtained from ovariectomized mice that had been treated with testosterone or control vehicle for 14 days. Samples were processed for the isolation of RNA, and analyzed for differentially expressed mRNAs using CodeLink Bioarrays and quantitative real-time PCR (qPCR) techniques. Data were compared to those obtained following testosterone treatment of orchiectomized mice, as well as after the administration of 17beta-estradiol and/or progesterone to ovariectomized mice.

RESULTS: Our findings demonstrate that testosterone regulates the expression of thousands of genes in the lacrimal and meibomian glands of ovariectomized mice. The magnitude and extent of these hormonal effects, which encompassed numerous biological, molecular, and cellular ontologies, was tissue-dependent. Particularly notable was the androgen stimulation of meibomian gland genes related to lipid metabolic pathways, and the suppression of genes associated with keratinization. Many of the genes regulated by testosterone in female tissues were identical to those controlled by androgens in male lacrimal and meibomian glands. However, some genes were modulated in a sex-specific manner. In addition, a number of the androgen-regulated genes in female glands were altered in the opposite direction by 17beta-estradiol and/or progesterone.

CONCLUSIONS: Our results support our hypothesis that sex steroids may induce sex-specific and/or opposite effects in the lacrimal and meibomian glands. Whether these actions contribute to the prevalence of dry eye remains to be determined.

Abstract: Using dry eye questionnaires to measure contact lens dry eye

The effectiveness of questionnaires in the determination of Contact Lens Induced Dry Eye.
Ophthalmic Physiol Opt. 2009 Sep;29(5):479-86.
Michel M, Sickenberger W, Pult H.

PURPOSE: This study investigates how well the recently introduced Ocular Comfort Index (OCI) and the more established McMonnies Dry Eye Index are able to detect contact lens induced dry eye (CLIDE).

METHODS: Seventy volunteer contact lens wearers (mean age = 28.7 +/- 8.0; 52 female, 18 male) were grouped as CLIDE positive or CLIDE negative depending on three sets of criteria: Method I: objective (tear meniscus height, lid parallel conjunctival folds, phenol red thread test and tear break-up time); Method II: objective and/or subjective [contact lens dry eye questionnaire (CLDEQ)] (i.e. being positive by Method I and/or Method III); Method III: subjective (CLDEQ). Symptoms were measured using the McMonnies Dry Eye Index and the OCI. Discrimination was analysed by the receiver operating characteristic (ROC) curves; positive predictive values (PPV) and cut-off values were calculated.

RESULTS: ROC results for Methods I and II were statistically significant only for the McMonnies (p = 0.008; p < 0.001; respectively). In Method III ROC results were statistically significant for both the McMonnies (p = 0.001) and OCI (p = 0.005). The McMonnies showed the best prediction of Method I [0.646/10.5 (PPV/cut-off value)], while the OCI gave the best predictability in Method III only (0.518/30.6).

CONCLUSION: A McMonnies scoring of > or = 10.5 or an OCI scoring of > or = 30.6 indicates CLIDE. The McMonnies performs better in prediction of CLIDE than the OCI.

Abstract: Comparing different artificial tears through rose tinted glasses

This study's bottom line is unsurprising but still significant and I appreciate seeing a study confirm what so many of us know in practice: Those OTC lubricants, well, there's a reason we're using them but there's not much to choose between most of them. The measure in this study however is rose bengal staining.

Efficacy of different dry eye treatments with artificial tears or ocular lubricants: a systematic review.
Ophthalmic Physiol Opt. 2009 Aug 14. [Epub ahead of print]
Doughty MJ, Glavin S.
Department of Vision Sciences, Glasgow-Caledonian University, Glasgow, G4 OBA Scotland, UK.
Purpose: To objectively review the outcome of clinical studies where rose bengal stain (RB) has been used as an outcome measure to assess the efficacy of artificial tears (AT) in patients with dry eye.

Methods: From peer-reviewed articles published between 1947 and 2008, information was sought on dry eye status, as reported using a grading scheme, after use of RB as a diagnostic test, before and after use of a specific regimen of artificial tears or ocular lubricants for approximately 30 days. Mean baseline scores and post-treatment scores were calculated, along with the net change and the percentage change in the RB scores.

Results: From a total of 33 suitable data sets, published between 1985 and 2006, the group mean pre-treatment RB score was 4.25 +/- 1.55 (+/-S.D.), which decreased to 2.84 +/- 1.24 after 30 days of treatment. This represented a net change of -1.43 (95% CI of -1.04 to -1.45). For use of traditional AT (saline, hypromellose, etc), the net change was -0.95, it was -1.33 for use of carbomer (polyacrylic acid) gels and -2.10 for hyaluronic acid (HA) products. These changes represented net improvements of 25.9 +/- 18.4%, 38.0 +/- 20.7% and 41.8 +/- 16.3% respectively. The greater change with HA was not associated with a lower final outcome score, but with higher pre-treatment scores.

Conclusions: Based on RB grading schemes used by numerous different clinicians over many years, treatment of dry eye with artificial tears or ocular lubricants can be expected to improve the condition of the exposed ocular surface. Assuming no improvement without treatment, a 30 days treatment period can be projected to produce an overall improvement of around 25%, but with no unambiguous statistical differences between product types.

Abstract: Dry eye state-of-the-nation

Literature review concluding that... we've come a long way, baby.

Etiology, prevalence, and treatment of dry eye disease.
Clin Ophthalmol. 2009;3:405-12. Epub 2009 Jul 14.
Gayton JL.
Eyesight Associates, Warner Robins, GA, USA.
PURPOSE: This review article examines the prevalence, etiology, and current therapies of dry eye disease, with special focus on postmenopausal women.

METHOD: A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry eye published prior to September 2008. The terms "dry eye" and "women" were searched in combination with one or more of the following words or phrases: prevalence, postmenopausal, etiology, risk factors, therapy, medications, surgery, tear film, and quality of life. Articles were selected based on their direct applicability to the subject matter. A manual search was also conducted based on citations in the published literature.

RESULTS: Epidemiologic studies identified prevalence rates ranging from 7% in the United States to 33% in Taiwan and Japan. Risk factors include advanced age, female sex, smoking, extreme heat or cold weather conditions, low relative humidity, use of video display terminals, refractive surgery, contact lens wear, and certain medications.

CONCLUSION: The last decade has brought about a better understanding of the etiology of dry eye disease. New therapies that can alleviate the signs and symptoms of dry eye disease and, consequently, improve the quality of life of dry eye patients are available in the market.

Abstract: Ocular surface injuries in autoimmune dry eye

Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness.
Histol Histopathol. 2009 Oct;24(10):1357-65.
Cejková J, Ardan T, Cejka C, Malec J, Jirsová K, Filipec M, Ruzicková E, Dotrelová D, Brunová B.

Autoimmune dry eye (Sjögren's syndrome, SS) is a chronic systemic disease characterized by salivary and lacrimal gland inflammation and tissue damage leading to keratoconjunctivitis sicca and xerostomia. In this review attention has been devoted to the cause of the development of oxidative injuries of the ocular surface of patients suffering from SS. It was shown that lacrimal glands and diseased conjunctival epithelium reveal increased expression of pro-inflammatory cytokines which are released into the tear fluid. A high amount of pro-inflammatory cytokines highly induce the elevated expression and activity of enzymatic systems that generate reactive oxygen and nitrogen species. An abundant amount of these toxic products leads to a decrease in antioxidants and to the formation of cytotoxic related oxidants, such as peroxynitrite. All these factors, together with reactive oxygen species from polymorphonuclear leukocytes, contribute to the development of oxidative injuries at the ocular surface. From the clinical point of view it is important that the level of severity of the above described microscopical disturbances found in conjunctival epithelial cells goes parallel with the level of severity of dry eye symptoms.

Abstract: Lacrisert

The length of treatment in this study is impressive compared to what one commonly sees in study of this type.

Extending the duration of tear film protection in dry eye syndrome: review and retrospective case series study of the hydroxypropyl cellulose ophthalmic insert.
Ocul Surf. 2009 Jul;7(3):154-62.
Wander AH, Koffler BH.
From the University of Cincinnati College of Medicine and Academic Health Center, Cincinnati, Ohio.

ABSTRACT Options for extending the duration of tear film protection in dry eyes include artificial tear formulations with enhanced viscosity/polymeric systems, ocular ointments and gels, and, recently, the hydroxypropyl cellulose ophthalmic insert (Lacrisert(R); distributed by Aton Pharma, Inc., Lawrenceville, NJ, USA). The goal in using these agents is to achieve a balance between maximizing tear film stability and ocular surface retention, while simultaneously maintaining or improving vision, comfort, and convenience. In this article, various agents are reviewed, and findings are presented from a retrospective study of patients who used hydroxypropyl cellulose ophthalmic inserts within the previous 2 years. The median length of therapy with the insert was 5.3 years, and nearly 65% of patients had used it for more than 2 years. Findings suggest that the hydroxypropyl cellulose ophthalmic insert is a relatively safe, tolerable, and effective therapy for dry eye, either alone or in conjunction with other therapies.

Abstract: AMT in SJS and TEN

Hm, perhaps we need a few more acronyms?

I am not a big fan of AMT in more common dry eye cases because I've so rarely heard from anyone who has been helped by it but in these severe cases I am so glad it's available. I hope that where people sclerals are also being tried on patients in such serious danger of sight-threatening dryness.

Amniotic Membrane Transplantation as a New Therapy for the Acute Ocular Manifestations of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
Surv Ophthalmol. 2009 Aug 20. [Epub ahead of print]
Shay E, Kheirkhah A, Liang L, Sheha H, Gregory DG, Tseng SC.
TissueTech Inc., Miami, Florida, USA.

Stevens-Johnson syndrome and its more severe variant, toxic epidermal necrolysis, have relatively low overall incidence; however, this disease presents with high morbidity and mortality. The majority of patients develop ocular inflammation and ulceration at the acute stage. Due to the hidden nature of these ocular lesions and the concentration of effort toward life-threatening issues, current acute management has not devised a strategy to preclude blinding cicatricial complications. This review summarizes recent literature data, showing how sight-threatening corneal complications can progressively develop from cicatricial pathologies of lid margin, tarsus, and fornix at the chronic stage. It illustrates how such pathologies can be prevented with the early intervention of cryopreserved amniotic membrane transplantation to suppress inflammation and promote epithelial healing at the acute stage. Significant dry eye problems and photophobia can also be avoided with this intervention. This new therapeutic strategy can avert the catastrophic ophthalmic sequelae of this rare but devastating disease.

Wednesday, September 9, 2009

Abstract: Sjogrens & mice...

Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice.
Am J Pathol. 2009 Sep;175(3):1136-47. Epub 2009 Aug 21.
Turpie B, Yoshimura T, Gulati A, Rios JD, Dartt DA, Masli S.
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA.

Thrombospondin-1 (TSP-1) is a major activator of latent transforming growth factor-beta in vitro as well as in vivo. Mice deficient in TSP-1, despite appearing normal at birth, develop a chronic form of ocular surface disease that is marked by increased apoptosis and deterioration in the lacrimal gland, associated dysfunction, and development of inflammatory infiltrates that result in abnormal tears. The increase in CD4(+) T cells in the inflammatory infiltrates of the lacrimal gland, and the presence of anti-Sjögren's syndrome antigen A and anti-Sjögren's syndrome antigen B antibodies in the serum resemble autoimmune Sjögren's syndrome. These mice develop an ocular surface disorder dry eye that includes disruption of the corneal epithelial layer, corneal edema, and a significant decline in conjuctival goblet cells. Externally, several mice develop dry crusty eyes that eventually close. The inflammatory CD4(+) T cells detected in the lacrimal gland, as well as those in the periphery of older TSP-1 null mice, secrete interleukin-17A, a cytokine associated with chronic inflammatory diseases. Antigen-presenting cells, derived from TSP-1 null, but not from wild-type mice, activate T cells to promote the Th17 response. Together, these results indicate that TSP-1 deficiency results in a spontaneous form of chronic dry eye and aberrant histopathology associated with Sjögren's syndrome.

Drug news: Resolvyx RX10045 positive results

Good news for Resolvyx on its fish oil derivative eye drop:

Resolvyx Reports Positive Results For Phase 2 Clinical Study Of RX-10045

Resolvyx has reported positive data from a phase 2 clinical study evaluating RX-10045, a resolvin administered as a topical eye drop for the treatment of patients with chronic dry eye syndrome.

In the 28-day, randomized, placebo-controlled, 232-patient trial, RX-10045 produced dose-dependent, improvement on the primary endpoints for both the signs and symptoms of dry eye. Alos, it was shown to be safe and well tolerated, said the company.

The phase 2 study examined three doses of RX-10045 and utilized a controlled adverse environment (CAE) to measure corneal staining in a stressful drying environment, as well as daily patient diaries using a standard visual analog scale to assess symptom improvement over the course of the study.

RX-10045 was superior to placebo on the primary symptomatic endpoint of Worst Symptom Score, as well as on several individual symptoms. The onset of symptom relief occurred within the first week of treatment and continued to improve over the course of the 28-day study, suggesting the potential for even greater benefit with longer treatment durations.
Moreover, RX-10045 also produced a 75% reduction from baseline in CAE-induced staining of the central cornea, the primary sign endpoint in the study. The improvement was greater than that observed for placebo, the difference approaching statistical significance.

Drug news: Pfizer's JAK-3 inhibitor

I've run across just a couple of bits and scraps about this but thought it looked interesting.

For background, Pfizer's JAK-e inhibitor is an immunosuppressant, ref. this recent abstract:

CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. (May 2009 study from Current Opinion in Investigative Drugs)

...And they seem to be further along with it clinically than others. Then tucked in a news clip on August 25:
In the area of dry eye, a JAK-3 inhibitor, originally investigated as a systemic medication for rheumatoid arthritis and transplant rejection, has been reformulated as a topical eye drop.

Sounds like a wannabe Restasis competitor if it comes together. I will be interested to see more on this one and will keep you posted.

Abstract: Cyclosporine-A and trachomatous dry eye

Ahhhh, thank you, it's great to get back to an abstract of a medical rather than a commercial study. Real data, real medical problem being treated. - Oh yes, remember the pre Restasis days when cyclosporine was used to treat severe dry eye? Here's a good example of why that was.

Efficacy of topical cyclosporine A in the treatment of severe trachomatous dry eye.
Clin Experiment Ophthalmol. 2009 Aug;37(6):541-9.
Guzey M, Karaman SK, Satici A, Ozardali I, Sezer S, Bozkurt O.
Department of Ophthalmology, Harran University School of Medicine, Sanliurfa, Turkey.

PURPOSE: The purpose of this study was to evaluate the efficacy of topical cyclosporine A (CsA) treatment in patients with severe trachomatous dry eye.

METHODS: Sixty-four severe trachomatous dry eye patients who had undergone Schirmer testing with topical anaesthetic measured 5 mm or less and a tear film break-up time (TFBUT) of 5 s or less were included in the study. Thirty-two patients were treated with CsA 0.05% ophthalmic emulsion twice daily and concomitant five times daily non-preserved artificial tear, and the other 32 patients who were designated as the control group received vehicle emulsion twice daily and non-preserved artificial tear five times daily. Pretreatment and post-treatment evaluations included subjective assessment of the patients (total symptoms scores and ocular surface disease index [OSDI] scores), Schirmer testing with topical anaesthesia, TFBUT, rose Bengal and fluorescein staining scores, conjunctival impression cytological scoring and goblet cell counting.

RESULTS: Following 6 months of CsA treatment, the differences between the pretreatment and post-treatment test results including total symptoms scores and OSDI scores, the rose Bengal and fluorescein staining scores, TFBUT values, and the Schirmer testing measurements were found to be statistically significant. Impression cytology also showed improvement of squamous metaplasia in 26 patients (81.25%) and increase in goblet cell density in 23 patients (71.88%).

CONCLUSIONS: Topical CsA was effective in the treatment of severe trachomatous dry eye, yielding improvements in both objective and subjective measurements with a safety profile.

Abstract: Lasik study (cough, choke)

If you didn't notice the date of this study or the word 'wavefront', you might be forgiven for having assumed it came straight out of the Dark Ages of LASIK in the 90s when the only thing anybody (well, any ophthalmologist) knew or cared much about was UCVA and BCVA after surgery.

I know the profession has made considerable progress since then in recognizing the significance of things like vision quality and ocular surface pain. So what gives here?

I don't know whether to laugh, cry or bust someone's chops (I'm inclining to the latter, I'm afraid) when I read in a study of this scope a dry eye rate of 0.18%. I recalculated it to make sure the decimal was in the right place.

You are seriously claiming to have seen no more dry eye in your patients than DLK?

You have got to be kidding me.

How'd you measure dry eye? ("Quick, stick a Schirmer strip in there while the anaesthetic drop is still sloshing around.")

The real explanation of course is in the abstract: "Complications were tabulated using all available data." In a study stating a dry eye rate far lower than almost any recent research would put it by almost any measure of dry eye symptoms and/or signs, I can only conclude that dry eye data was unavailable for the majority of these patients because no one bothered to gather it.

One-month outcomes of wavefront-guided LASIK for low to moderate myopia with the VISX STAR S4 laser in 32,569 eyes.
Schallhorn SC, Venter JA.

J Refract Surg. 2009 Jul;25(7 Suppl):S634-41.

PURPOSE: To determine the safety and efficacy of wavefront-guided LASIK for the correction of low to moderate myopia, as performed by surgeons employed by Optical Express, a large corporate provider.

METHODS: Data were extracted from the Optical Express central database on 22,900 patients (42,143 eyes) who underwent primary LASIK to treat low to moderate myopia and/or astigmatism. All treatments used a wavefront-guided ablation profile and had a refractive target of emmetropia. Outcomes were evaluated using 1-month follow-up data, which were available for 32,569 eyes of 17,713 patients (77% follow-up). Complications were tabulated using all available data.

RESULTS: The mean manifest spherical equivalent (MSE) was reduced from -2.97 +/- 1.33 diopters (D) (range: -0.37 to -6.00 D) to -0.03 +/- 0.29 D (range: -3.50 to +4.50 D) 1 month after surgery. Ninety-four percent of eyes were within 0.50 D of the intended correction, and the correlation coefficient of the attempted versus achieved MSE was 0.96. Uncorrected visual acuity (UCVA) of 20/20 or better was achieved in 92% of eyes; 99% of eyes achieved UCVA of 20/40 or better. Among patients who had bilateral laser vision correction, 98% achieved 20/20 uncorrected binocular vision. Average best spectacle-corrected visual acuity (BSCVA) improved slightly 1 month after surgery (mean change: +0.01 logMAR). There were 210 (0.67%) eyes that lost 2 or more lines of BSCVA; however, all eyes were 20/40 or better. Intraoperative complications occurred in 25 eyes (0.06%; 1:1686), and postoperative complications occurred in 210 eyes (0.64%; 1:155). The most common complications were dry eye (n=58; 0.18%; 1:562) and mild diffuse lamellar keratitis (grade 1 or 2) (n=58; 0.18%; 1:562).

CONCLUSIONS: Wavefront-guided LASIK can safely and effectively correct low to moderate myopia, as demonstrated by 1-month postoperative visual outcomes from a large number of patients.

Abstract: iTRAQ technology and tear fluid biomarkers

In the endless stream of studies trying to get closer to pinning down What Is A Dry Eye, I thought this one was very interesting.

Identification of Tear Fluid Biomarkers in Dry Eye Syndrome Using iTRAQ Quantitative Proteomics.
J Proteome Res. 2009 Aug 25. [Epub ahead of print]
Zhou L, Beuerman RW, Chan CM, Zhao SZ, Li XR, Yang H, Tong L, Liu S, Stern ME, Tan D.

The proteins found in tears have an important role in the maintenance of the ocular surface and changes in the quality and quantity of tear components reflect changes in the health of the ocular surface.

In this study, we have used quantitative proteomics, iTRAQ technology coupled with 2D-nanoLC-nano-ESI-MS/MS coupled to a statistical model to uncover proteins that are significantly and reliably changed in the tears of dry eye patients in an effort to reveal potential biomarker candidates.

Fifty-six patients with dry eye and forty healthy subjects were recruited for this study. In total 93 tear proteins were identified with a ProtScore >= 2 (>= 99% confidence). Associated with dry eye were 6 up-regulated proteins, alpha-enolase, alpha-1-acid glycoprotein 1, S100 A8 (calgranulin A), S100 A9 (calgranulin B), S100 A4 and S100 A11 (calgizzarin) and 4 down-regulated proteins, prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Receiver operating curves (ROC) were evaluated for individual biomarker candidates and a biomarker panel. Using a 4-protein biomarker panel, the diagnostic accuracy for dry eye was 96% (sensitivity: 91.0%; specificity: 90.0%).

Two biomarker candidates (alpha-enolase and S100 A4) generated from iTRAQ experiments were successfully verified using an ELISA assay. The levels of these 10 tear proteins reflect aqueous secretion deficiency by lacrimal gland, inflammatory status of the ocular surface. The clinical classification of the severity of the dry eye condition was successfully correlated to the proteomics by using four proteins that are associated with inflammation, alpha1-acid glycoprotein 1, S100 A8 and S100 A9. The nine tear protein biomarker candidates (except alpha1-acid glycoprotein 1) were also verified using an independent age-matched patient sample set. This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.

Eyewear: Gunnar Optiks?

I just ran across this site and found it interesting. Going to try to get some samples to test out.

Gunnar Optiks - lens technology page

The highly wrapped configuration creates an ocular microclimate trapping in humidity and blocking out evaporative air currents.

They're speaking my language. How often do I run across an optical company that uses phrases like this? Delightful. I'll let you know what comes of it if anything.