Saturday, March 5, 2011

Abstract: PCOS and dry eye

Effects of hyperandrogenism on tear function and tear drainage in patients with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by chronic anovulation and hyperandrogenism. Hormonal changes can affect ocular surface and tear functions. We evaluated dry eye symptoms, clinical tear film alterations, and tear clearance in patients with PCOS.

STUDY DESIGN: Thirty-five women with PCOS and 22 healthy individuals were enrolled in the study. An ocular surface disease index (OSDI) questionnaire was administered, and after the routine ophthalmologic examination tear film breakup time (TBUT) and Schirmer tests were performed. Tear clearance was assessed via fluorescein dye disappearance test (FDDT).

RESULTS: No difference was observed in Schirmer test between the groups, however OSDI scores were significantly higher (p = 0.01) and TBUT was significantly lower (p = 0.01) in PCOS patients than in the control women. FDDTs were not different between the PCOS and control subjects.

CONCLUSION: Our findings suggest that patients diagnosed with PCOS should be advised to obtain an ophthalmic examination, especially for dry eye.

J Reprod Med. 2011 Jan-Feb;56(1-2):65-70.
Coksuer H, Ozcura F, Oghan F, Haliloglu B, Karatas S.
Department of Obstetrics and Gynecology, Dumlupinar University School of Medicine, Kutahya, Turkey.

Abstract: Green tea and the corneal epithelium

Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells.

PURPOSE: To determine the anti-inflammatory and anti-oxidant effects of epigallocatechin gallate (EGCG), the major polyphenol component of green tea, in human corneal epithelial cells (HCEpiC).

METHODS: HCEpiC were challenged with interleukin-1β (IL-1β) for 18 h or hyperosmolarity (440 mOsm) for 24 h. Luminex technology was used to determine the effects of EGCG (0.3 - 30 µM) on IL-1β- or hyperosmolar-induced cytokine release into the medium. Cell metabolic activity was measured using the alamarBlue assay. Effects of EGCG on mitogen-activated protein kinase (MAPK) phosphorylation were determined by cell-based enzyme-linked immunosorbent assay (ELISA) and western blotting. Effects of EGCG on nuclear factor kappa B (NFκB) and activator protein-1 (AP-1) transcriptional activity were assessed by reporter gene assay. The effects of EGCG on glucose oxidase (GO)-induced reactive oxygen species (ROS) production was determined using the ROS probe CM-H(2)DCFDA.

RESULTS: Treatment of HCEpiC with 1 ng/ml IL-1β for 18 h significantly increased release of the cytokines/chemokines granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1), while hyperosmolarity-induced release of IL-6 and MCP-1. When cells were treated with IL-1β and EGCG or hyperosmolarity and EGCG there was a dose-dependent reduction in release of these cytokines/chemokines, with significant inhibition observed at 3-30 µM. There was no effect of EGCG on cell metabolic activity at any of the doses tested (0.3-30 µM). EGCG significantly inhibited phosphorylation of the MAPKs p38 and c-Jun N-terminal kinase (JNK), and NFκB and AP-1 transcriptional activities. There was a significant dose-dependent decrease in GO-induced ROS levels after treatment of HCEpiC with EGCG.

CONCLUSIONS: EGCG acts as an anti-inflammatory and anti-oxidant agent in HCEpiC and therefore may have therapeutic potential for ocular inflammatory conditions such as dry eye.

Mol Vis. 2011 Feb 18;17:533-42.
Cavet ME, Harrington KL, Vollmer TR, Ward KW, Zhang JZ.
Global Pharmaceutical R&D, Bausch + Lomb, Rochester, NY.

Wednesday, March 2, 2011

Abstract: Another eyeball & tear film model

Simultaneous examination of tear film break-up and the lipid layer of the human eye: a novel model eye for time course simulation of physiologic tear film behavior (Part 2).

This article describes a model eye created to mimic the three-layered human tear-film. The model replicates the properties of the mucin, liquid and lipid layer as well as the time-course behavior including blinking process and tear film break-up for measurements with the tear film sensor described in Part 1. The setup basically consists of a sphere that is moistened by a dilution of tear film substitute. Therefore, the time point of the first break-up strongly depends on the consistency of the dilution. By means of an integrated heater, the evaporation rate of the artificial tear-film can be increased. To illustrate the applicability of the model eye, exemplary images during tear-film simulation, taken with and without using the heater, are shown. All images were captured by the sensor. Results and other potential applications are briefly discussed.

Z Med Phys. 2010;20(4):316-9. Epub 2010 Sep 29.
Arnold S, Bruenner H, Langenbucher A.
Medical Optics at the Institute of Medical Physics, University of Erlangen-Nuremberg, Erlangen, Germany.

Abstract: Inflammatory mediators and goblet sell secretions

Way way way over my head, but I like anything resolving inflammation, within reason...

Conjunctival Goblet Cell Secretion Stimulated by Leukotrienes Is Reduced by Resolvins D1 and E1 To Promote Resolution of Inflammation.

The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are goblet cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased goblet cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival goblet cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT(1) and CysLT(2,) were present in rat conjunctiva and in rat and human cultured conjunctival goblet cells. All leukotrienes LTB(4), LTC(4), LTD(4), and LTE(4), as well as PGD(2), stimulated goblet cell secretion in rat goblet cells. LTD(4) and LTE(4) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), and LTD(4) activated ERK1/2. The CysLT(1) receptor antagonist MK571 significantly decreased LTD(4)-stimulated rat goblet cell secretion and the increase in [Ca(2+)](i). Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD(4)-stimulated goblet cell secretion in cultured rat goblet cells. LTD(4)-induced secretion from human goblet cells was blocked by RvD1. RvD1 and RvE1 prevented LTD(4)- and LTE(4)-stimulated increases in [Ca(2+)](i), as well as LTD(4) activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival goblet cell mucous secretion with LTD(4) using the CysLT(1) receptor. Stimulated secretion is terminated by preventing the increase in [Ca(2+)](i) and activation of ERK1/2 by RvD1 and RvE1.

J Immunol. 2011 Feb 28. [Epub ahead of print]
Dartt DA, Hodges RR, Li D, Shatos MA, Lashkari K, Serhan CN.
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114;

GlobalData dry eye market forecast

Dry Eye Syndrome Therapeutics - Pipeline Assessment and Market Forecasts to 2017
February 28, 2011

GlobalData forecasts the global dry eye syndrome therapeutics market to grow at 6.3% annually for the next seven years, to reach $2.8 billion by 2017. It was valued at $1,858m in 2010. This significant growth is primarily attributed to increasing therapeutic options for the treatment of dry eyes. In addition, the successful launch of some of the targeted therapies such as rebamipide and Remura (bromfenac), currently in NDA (New Drug Application) filing stage, may significantly stimulate market growth in the near future. However, the low prescription rate and non-adherence to medication will continue to be a barrier for market growth.

GlobalData analysis points out that the current competition in the dry eye syndrome therapeutics market is weak, and available treatment options have been moderately successful in meeting market demand. The products currently available in the market provide only symptomatic relief. The current marketed products, except Restasis, treat only the symptoms of the disease. As the products currently available do not serve the market’s unmet needs, the market continues to present opportunities for stronger pipeline candidates. The extent of unmet needs in the dry eye syndrome therapeutics market is considered to be at a high level and can be fulfilled by technologically advanced products possessing improved safety and efficacy profiles which are disease targeting. The only available prescription drug, Restasis, has proven its success as is evident by the increasing yearly sales from the year of launch. This paves the way for the entry of new products which aim to treat the disease and not just provide symptom relief.

GlobalData found that there are more than 35 products in different stages of development. Remura and rebipamide, currently in NDA Filing and Phase III, are the most promising products in the pipeline. Remura and rebipamide have shown encouraging response rates in pretreated patients and have great potential in the dry eye syndrome therapeutics market. If approved, other pipeline candidates such as CF101, Cyclokat and SF102, currently in Phase III, will provide alternative treatment options to current therapies. These products are expected to meet some of the unmet needs and will provide physicians with a better choice in treating dry eye syndrome. They may also lead to an intensely competitive market. In summary, the global dry eye syndrome therapeutics market is heading towards a highly competitive landscape.

Abstract: Systemic ivermectin for ocular demodex

Clinical Treatment of Ocular Demodex folliculorum by Systemic Ivermectin.

PURPOSE: To report clinical outcomes of the treatment of ocular Demodex folliculorum with oral ivermectin.

DESIGN: Noncomparative, interventional case series.

METHODS: Setting. Institutional. Study Population. Twenty-four eyes of 12 patients (3 male and 9 female; mean age ± standard deviation, 50.4 ± 21.0 years) with refractory posterior blepharitis with the presence of D. folliculorum in lash samples were enrolled in this study. Intervention. Patients were instructed to take 1 dose of oral ivermectin (200 μg/kg). All patients were instructed to repeat the treatment after 7 days. Main outcome measures. Tear meniscus height, Schirmer I test results, noninvasive tear film break-up time (BUT), quantification of the absolute number of D. folliculorum found in the lashes, and corneal fluorescein and rose bengal staining scores were obtained from all patients 1 day before and 28 days after treatment.

RESULTS: Statistical improvement was observed in the absolute number of D. folliculorum found in the lashes after the treatment with oral ivermectin. Average values of Schirmer I test results and tear film break-up time improved statistically after the treatment of oral ivermectin. No statistical improvement was observed in average lacrimal meniscus height or value of corneal fluorescein and rose bengal staining after treatment with oral ivermectin.

CONCLUSIONS: Ivermectin successfully reduced the number of D. folliculorum found in the lashes of patients with refractory blepharitis. Oral ivermectin may be very useful as a complement in the treatment of D. folliculorum infestation with ocular manifestation, especially in cases of unsuccessful treatment related to patient compliance.

Am J Ophthalmol. 2011 Feb 18. [Epub ahead of print]
Holzchuh FG, Hida RY, Moscovici BK, Villa Albers MB, Santo RM, Kara-José N, Holzchuh R.
Department of Ophthalmology, Hospital das Clínicas of University of São Paulo, School of Medicine, São Paulo, Brazil; Department of Ophthalmology, Santa Casa de São Paulo, São Paulo, Brazil.

Abstract: New diagnostic - TSAS

So many new diagnostic tools & techniques being reported on lately I can't even keep them all straight.

Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients.

PURPOSE: To evaluate tear film stability in patients with tear dysfunction and an asymptomatic control group by using the novel, noninvasive Tear Stability Analysis System (TSAS).

METHODS: In this prospective case-control study, 45 patients with dysfunctional tear syndrome (DTS) were stratified into three groups (1, 2, and 3/4) based on clinical severity, with higher scores indicating more severe symptoms; 25 asymptomatic control subjects were evaluated. TSAS measurements were performed with the RT-7000 Auto Refractor-Keratometer (Tomey Corporation, Nagoya, Japan). Images of ring mires projected onto the cornea every second for 6 seconds were captured and analyzed. Focal changes in brightness were calculated as numerical ring breakup (RBU) values, and the elapsed time when the cumulative values (RBU sum) exceeded a threshold was defined as the ring breakup time (RBUT).

RESULTS: RBUTs in the DTS groups were all significantly lower than those in the control subjects, with the lowest values found in DTS 3/4. RBUT was significantly shorter in DTS 3/4 than in DTS 1 (P < 0.001). The change in RBU sum over a 6-second period in the DTS groups combined or between the individual groups was statistically significant (P < 0.001), as was the difference between the 1- and 6-second values. For distinguishing between asymptomatic controls and DTS, the sensitivity and specificity of a 5.0-second RBUT cutoff were 82.0% and 60.0%, respectively.

CONCLUSIONS: The TSAS may be a useful, noninvasive instrument for evaluating tear stability and for classifying DTS severity.

Invest Ophthalmol Vis Sci. 2011 Jan 21;52(1):456-61. Print 2011.
Gumus K, Crockett CH, Rao K, Yeu E, Weikert MP, Shirayama M, Hada S, Pflugfelder SC.
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA.

Tuesday, March 1, 2011

Abstract: Visual performance impairment in dry eye

Impaired visual performance in patients with dry eye.

ABSTRACT Patients with dry eye disease (DED) often complain about poor vision, which is not easily quantifiable. This review assesses the current understanding of clinical evaluations of visual function in patients with DED. Several noninvasive techniques for the assessment of visual performance have been utilized in patients with DED, and these are critically reviewed in relation to the visual symptoms experienced by these patients. It is clear that none of the current techniques is ideal, and there is not one appropriate, simple, clinical test that can be used for assessing visual impairment in patients with DED. Evidence from a comprehensive literature search combined with clinical experience have been used to identify which tests are currently of most benefit and to highlight the future development of a more specific clinical test for visual impairment in the dry eye patient.

Ocul Surf. 2011 Jan;9(1):42-55.
Ridder WH, Tomlinson A, Huang JF, Li J.
From the Southern California College of Optometry, Fullerton, CA, USA.

Abstract: New diagnostic - Ocular Surface Thermographer

Who woulda thunk. Very interesting. So a dry eye cools off faster than a healthy eye when you're holding it open. And this decrease "correlated significantly" with TBUT - but presumably not Schirmer I and staining.

Screening for Dry Eye with Newly Developed Ocular Surface Thermographer.

PURPOSE: To evaluate the newly developed Ocular Surface Thermographer (TOMEY Corporation) for dry eye screening.

DESIGN: Prospective, controlled study.

METHODS: We studied 30 eyes of 30 patients diagnosed with dry eye (mean age ± standard deviation, 52.9 ± 17.1 years) and 30 eyes of 30 normal subjects (42.7 ± 17.0 years). The ocular surface temperature was measured immediately after eye opening and every second during 10 seconds of eye opening. The reliability of the measurements was determined by calculating intraclass correlation coefficients. Then, the correlations between the change in the ocular surface temperature and tear film break-up time, Schirmer I test values, and fluorescein staining scores were determined.

RESULTS: The measurements of the ocular surface temperature had a high degree of reliability. Immediately after eye opening, the temperature in the dry eye did not differ significantly from that in normal eyes in any of the 3 regions tested. The decrease in the ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P < .001) at 10 seconds after eye opening. The decrease in the temperature of the cornea was correlated significantly with the tear film break-up time (r = -0.572; P < .001). When the changes in ocular surface temperature of the cornea were used as an index for dry eye, the sensitivity was 0.83 and the specificity was 0.80 after 10 seconds.

CONCLUSIONS: Measurements of the ocular surface temperature obtained with our newly developed Ocular Surface Thermographer after 10 seconds of eye opening may provide a simple, noninvasive screening test for dry eyes.

Am J Ophthalmol. 2011 Feb 16. [Epub ahead of print]
Kamao T, Yamaguchi M, Kawasaki S, Mizoue S, Shiraishi A, Ohashi Y.
Department of Ophthalmology, Medicine of Sensory Function, Ehime University Graduate School of Medicine, Toon, Japan.

Abstract: SJS and TEN - ophthalmic sequelae

What these terrible conditions do to the eyes is nasty, nasty, nasty in every way. Awful thinking of people dealing with this without access to the kinds of treatments & tools that would help them regain some quality of life.

[Stevens-Johnson and Lyell syndromes: Mucocutaneous and ocular sequels in 43 cases.]

The ophthalmic sequelae of Stevens-Johnson and Lyell syndromes are deemed serious, and their mucocutaneous syndromes can adversely affect social and functional outcomes. The aim of this study is to describe these sequelae in Morocco.

This retrospective study involved all patients hospitalized in the dermatology department of the Ibn Rochd University Hospital in Casablanca for toxic epidermal necrolysis or Stevens-Johnson syndrome (SJS). The study period lasted from January 1986 to December 2006. Mucosal, cutaneous and ocular sequelae of these diseases were identified during follow-up.

During this 21-year period, 43 cases of Lyell syndrome and SJS were analyzed. Twenty-five women and 18 men were included and the average age was 28 years. Clinical forms were as follow: Lyell's syndrome: 32 cases; SJS: six cases; intermediary Lyell-SJS form: five cases. Average follow-up was 3 years. Concerning mucocutaneous sequelae, 72% of patients had diffuse hyperchromic macules with scarring, photosensitivity was noted in 70% of cases, telogen effluvium was seen in 10 cases, abnormal sweating was noted in eight cases, nail loss was seen in eight cases, and vaginal bands were noted in two cases. In the chronic phase, 70% of patients had photophobia with chronic lacrimation. Eyelid malposition was noted in 21% of cases: ectropion (n=6), entropion with trichiasis (n=3) and symblepharon in 13 cases (30%). Corneal complications involving superficial punctate keratitis were noted in 42% of cases and were associated with corneal neovascularisation in five cases. Finally, bilateral dry eye syndrome was seen in 24 cases (56%).

CONCLUSION: Our study confirms the reality of ocular, and mucocutaneous sequelae of Stevens-Johnson and Lyell syndromes. Ocular sequelae are dramatic, while cutaneous sequelae are unsightly. These sequelae have marked repercussions on the social and professional integration of our patients, most of whom were young.

Ann Dermatol Venereol. 2011 Feb;138(2):88-92. Epub 2010 Dec 15.
[Article in French]
Fellahi A, Zouhair K, Amraoui A, Benchikhi H.
Service de dermatologie-vénéréologie, CHU Ibn Rochd, Casablanca, Maroc.

Abstract: Delivering phospholipids via contact lens


And the search goes on... for the perfect contact lens technology that will make an unhealthy ocular surface impervious to the presence of a big foreign object. Well, good luck with that, I guess.

Loading and Release of a Phospholipid From Contact Lenses.

Dry eye syndrome has been associated with the lack of phospholipids in the tear film, leading to disruption of the tear film and subsequent irritation. This study explores the feasibility of loading a phospholipid into contact lenses for controlled release to the eye.

Silicone hydrogel contact lenses were loaded with 33 μg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. The loaded lenses were soaked at 35°C in either water or artificial tear solution (ATF), and the elution of DMPC was quantified by scintillation counting.

About 33 μg of DMPC was loaded into the lenses. An average of nearly 1 μg of DMPC was eluted into ATF within the first 10 h. Elution was about five times faster in ATF than in water. The elution appears to be controlled by the diffusivity of DMPC in the contact lens and the properties of the elution solution.

This type of lens technology may have the potential to deliver phospholipids to help address contact lens-related dryness through lipid layer stabilization.

Optom Vis Sci. 2011 Feb 17. [Epub ahead of print]
Pitt WG, Jack DR, Zhao Y, Nelson JL, Pruitt JD.
*PhD †BS ‡MS Chemical Engineering Department, Brigham Young University, Provo, Utah (WGP, DRJ, YZ), and CIBA VISION Corporation, Global Research, Duluth, Georgia (JLN, JDP).

Abstract: Antioxidant content and UV absorption characteristics of human tears

Antioxidant Content and Ultraviolet Absorption Characteristics of Human Tears.

Dry eye syndrome is a common age-related disorder, and decreased antioxidant/ultraviolet (UV) radiation protection in tears may be part of the cause. This study aimed to compare the tear antioxidant content and flow rate in young and older adults. The total antioxidant content and UV absorbing properties of various commercially available ophthalmic solutions used to alleviate dry eye symptoms were also examined.

Minimally stimulated tears were collected from 120 healthy Chinese adults with no ocular pathology. Two age groups were studied: 19 to 29 years (n = 58) and 50 to 75 years (n = 62). Tear samples from each subject and 13 ophthalmic solutions were analyzed for total antioxidant content (as the Ferric Reducing/Antioxidant Power value). Tear flow rates were estimated from time taken to collect a fixed volume of tear fluid. UV absorbance spectra of pooled fresh reflex tear fluid and the ophthalmic solutions were determined.

Results showed that the antioxidant content of minimally stimulated tears from older subjects (398 ± 160 μmol/l) was not significantly lower than that of younger subjects (348 ± 159 μmol/l; p = 0.0915). However, there was a significant difference in the tear flow rates between the two groups (p < 0.0001), with the younger group having three to four fold higher flow rate. None of the commercial preparations tested had detectable antioxidant content, and none showed the UV absorption characteristics of natural reflex tears.

The effect of low flow rate on the dynamic antioxidant supply to the corneal surface indicates that older subjects have poorer overall defense against photooxidative and other oxidative processes. This could predispose older persons to corneal stress and development of dry eye syndrome. The commercially available artificial tears tested lack both the antioxidant content and UV absorbing characteristics of natural tears. Artificial tears formulations that help restore natural antioxidant and UV absorbing properties to the tear film of the aging eye may help prevent or improve dry eye symptoms and promote ocular health.

Optom Vis Sci. 2011 Feb 17. [Epub ahead of print]
Choy CK, Cho P, Benzie IF.
*BSc(Hons), PhD. †BOptom, PhD ‡DPhil, FIBMS, CSci School of Optometry (CKMC, PC), and Department of Health Technology and Informatics (IFFB), The Hong Kong Polytechnic University, Hong Kong SAR, China.