Tuesday, March 22, 2011

Abstract: What those lid wipers look like

The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: an in vivo confocal and histological study.

The inner border of the eyelid margin is critically important for ocular surface integrity because it guarantees the thin spread of the tear film. Its exact morphology in the human is still insufficiently known. The histology in serial sections of upper and lower lid margins in whole-mount specimens from 10 human body donors was compared to in vivo confocal microscopy of eight eyes with a Heidelberg retina-tomograph (HRT II) and attached Rostock cornea module. Behind the posterior margin of the Meibomian orifices, the cornified epidermis stopped abruptly and was replaced by a continuous layer of para-keratinized (pk) cells followed by discontinuous pk cells. The pk cells covered the muco-cutaneous junction (MCJ), the surface of which corresponded to the line of Marx (0.2-0.3 mm wide). Then a stratified epithelium with a conjunctival structure of cuboidal cells, some pk cells, and goblet cells formed an epithelial elevation of typically about 100 μm initial thickness (lid wiper). This continued for 0.3-1.5 mm and formed a slope. The MCJ and lid wiper extended all along the lid margin from nasal to temporal positions in the upper and lower lids. Details of the epithelium and connective tissue were also detectable using the Rostock cornea module. The human inner lid border has distinct zones. Due to its location and morphology, the epithelial lip of the lid wiper appears a suitable structure to spread the tear film and is distinct from the MCJ/line of Marx. Better knowledge of the lid margin appears important for understanding dry eye disease and its morphology can be analysed clinically by in vivo confocal microscopy.

J Anat. 2011 Apr;218(4):449-61. doi: 10.1111/j.1469-7580.2011.01355.x.
Knop E, Knop N, Zhivov A, Kraak R, Korb DR, Blackie C, Greiner JV, Guthoff R.
Ocular Surface Center Berlin, Department for Cell and Neurobiology, Center for Anatomy, Charité- Universitätsmedizin Berlin, Berlin, Germany University Eye Hospital Rostock, Rostock, Germany Korb Associates, Boston, MA, USA The Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Abstract: Physical barrier vs. drops

Effectiveness of polyethylene covers versus carbomer drops (Viscotears(®) ) to prevent dry eye syndrome in the critically ill.

The purpose of this study was to compare the effectiveness of the polyethylene covers versus carbomer eye drops to prevent dry eye syndrome in intensive care unit patients.

Concerns about eye care for critically ill patients remain an issue. Few studies have focused on the effect of polyethylene covers and eye drops. In addition, there are no studies comparing polyethylene covers and carbomer eye drops for critically ill patients. Design.  A prospective, randomised and contralateral eye study was conducted.

The study took place in an intensive care unit in 2007. Thirty-six eyes of 18 patients, who were under mechanical ventilation or unconscious for more than 24 hours in the intensive care unit, were studied. After examining the eyes of the patients with the Schirmer 1 test and fluorescein dye test, suitable patients were included in the study. One eye of the patient was randomly covered with a polyethylene cover every 12 hours, and carbomer drops were instilled on the other eye every six hours. All eyes were checked for an ocular surface abnormality by the same ophthalmologist everyday. The study interventions were continued until a defect was detected or for five days. Patients with a defect detected completed the study and were recorded as positive for the primary endpoint.

Carbomer drop was effective in prophylaxis of dry eye syndrome in only three of 18 patients, whereas polyethylene cover showed greater effect in 18 of 18 eyes at the end of the study (SD 0·3835, Z = -3·873, p < 0·001). A negative effect of greater rima palpebra in the resting position was observed in the efficacy of carbomer drop (r = -0·476, p < 0·05).

Conclusion.  This study suggests that a polyethylene cover is significantly effective in prevention of dry eye syndrome in intensive care patients. As an eye care intervention, the effectiveness of polyethylene cover should be supported by further studies. Relevance to clinical practice.  This study, which is an initial step in preventing dry eye syndrome in critically ill patients, also offers a new and effective eye care method in these patients.

J Clin Nurs. 2011 Mar 17. doi: 10.1111/j.1365-2702.2010.03559.x. [Epub ahead of print]
Kocaçal Güler E, Eşer I, Eğrilmez S.
Authors: Elem Kocaçal Güler, MSc, RN, Research Assistant, Fundamentals of Nursing Department, Ege University School of Nursing; İsmet Eşer, PhD, RN, Professor, Fundamentals of Nursing Department, Ege University School of Nursing; Sait Eğrilmez, PhD, Medical Doctor, Associate Professor, Opthalmology Department, Ege University School of Medicine, İzmir, Turkey.

Abstract: The old signs vs symptoms question

Lack of concordance between dry eye syndrome questionnaires and diagnostic tests.

PURPOSE: To report the prevalence of dry eye syndrome (DES) in a subset of patients > 50 years old in Valladolid, Spain, calculate internal validity of two DES screening questionnaires, and correlate the results with DES diagnostic tests.

METHODS: Patients > 50 years-old were randomly selected from the medical network census in Valladolid; they answered the modified McMonnies questionnaire (Q1) and the Ocular Surface Index questionnaire (Q2) and then underwent an ophthalmic evaluation which included: tear break-up time (TBUT), fluorescein and Rose Bengal staining, and Schirmer with anesthesia were performed. Descriptive analysis, test concordance analysis, and Q1 and Q2 reliability using ROC curves were performed.

RESULTS: A total of 270 subjects (58.2% female; 41.8% male) with an average age of 64.5 years (95% CI: 63.3 - 65.7) were enrolled. The prevalence of DES based on the Schirmer-Tear break-up time tests combination was 24.2%. The mean Q1 score was 1.2, and 1.4 for Q2. Grittiness and discomfort in dry environments (28.9%) were the most common symptoms recorded for Q1. For Q2 "grittiness" (99.2%) and "burning sensation" (98.9%)were the most common symptoms. With the Schirmer-TBUT combination, DES prevalence in Valladolid was 24.2%, 45.8% with TBUT, and 45.6% with Schirmer test. Values for the areas under the ROC curve for Q1, Q2, and most objective tests were < 0.5, except for Q2 and TBUT (0.503). Cronbach alpha was > 0.7 for all Q1 and Q2 items. Statistically significant concordance was reported for Schirmer - TBUT (κ=0.14) and TBUT- fluorescein staining (κ=0.09); (P<0.05).

CONCLUSIONS: Q1 and Q2 were unreliable for DES diagnosis and showed poor internal consistency. Fluorescein and Rose Bengal staining were the most concordant tests for DES diagnosis. Finally, there was no correlation between either screening questionnaire and objective DES diagnostic tests.

[Article in English, Spanish]Arch Soc Esp Oftalmol. 2011 Jan;86(1):3-7. Epub 2011 Feb 19.
Fuentes-Páez G, Herreras JM, Cordero Y, Almaraz A, González MJ, Calonge M.
Asociación Para Evitar La Ceguera en México, México D.F, México.

Abstract: Twice daily to once daily Restasis

The Effect of Decreasing the Dosage of Cyclosporine A 0.05% on Dry Eye Disease After 1 Year of Twice-Daily Therapy.
PURPOSE: To evaluate the effect of decreasing topical cyclosporine 0.05% (tCSA) (Restasis; Allergan, Irvine, CA) from twice-daily dosing to once-daily dosing in patients who have already completed 12 months of twice-daily therapy for dry eye disease.

DESIGN: Prospective, randomized, single-masked, parallel group comparison.

PARTICIPANTS: One hundred patients who had already been treated with tCSA twice daily for more than 1 year were randomized either to continue tCSA twice daily (n = 50) or to decrease tCSA once daily (n = 50).

METHODS: Clinical measurement of dry eye variables was performed for all patients at baseline, 3 months, and 6 months. Mean data were used for within-group (longitudinal analysis) and between-group comparisons (once daily vs. twice daily).

MAIN OUTCOME MEASURES: Fluorescein tear break-up time, corneal fluorescein staining score, lissamine green staining score, Schirmer tear test, and ocular surface disease index.

RESULTS: At the end of the study, patients whose treatment dose was decreased to once daily demonstrated statistically significant improvement in tear break-up time [4.13 seconds (n = 37) vs. 3.11 seconds at baseline (n = 50); P = 0.0003] and lissamine green staining score [4.42 (n = 37) vs. 6.51 at baseline (n = 50); P = 0.024]; fluorescein staining score, Schirmer test results, and ocular surface disease index did not change significantly (P > 0.05). Furthermore, the once-daily group demonstrated significantly superior ocular surface disease index compared with the twice daily group [15.91 (n = 37) vs. 22.62 (n = 48); P = 0.0496]. The remaining outcome measures between once daily and twice daily were not significantly different (P > 0.05). Seven of 50 patients (14%) in the once-daily group (vs. 0% in the twice-daily group) ended the study early because of worsening dry eye symptoms (P < 0.05) and went back to twice-daily dosing.

CONCLUSIONS: For patients with dry eye that has been controlled with tCSA twice daily for at least 1 year, decreasing to tCSA once daily may still allow suppression of the dry eye disease.

Cornea. 2011 Mar 14. [Epub ahead of print]
Su MY, Perry HD, Barsam A, Perry AR, Donnenfeld ED, Wittpenn JR, Dʼaversa G.
From the Ophthalmic Consultants of Long Island, Nassau University, Rockville Centre, NY.

Abstract: Effects of sodium hyaluronate measured by TSAS

[Sustained effects of sodium hyaluronate solution on tear film stability evaluated by Tear Stability Analysis System].
[Article in Japanese]

PURPOSE: To investigate the sustained effects of sodium hyaluronate solution (HA) on tear film stability using a Tear Stability Analysis System (TSAS), a method enabling quantitative evaluation of tear film stability.

METHODS: Eighteen eyes of 18 normal subjects (N group) and 21 eyes of 21 dry eye patients (D group) were examined. Dry eye was diagnosed by the 2006 diagnostic criteria. In each subject, artificial tears (AT), 0.1% sodium hyaluronate solution (H 01) or 0.3% sodium hyaluronate solution (H 03) were instilled into both eyes, and tear film stability in the right eye before and 1, 5, 15, 30, 60 and 120 minutes after instillation was compared using a break up index (BUI: 0-100), the TSAS's index of tear film stability.

RESULTS: N group: In both the AT and H 01 subgroups, no significant change was found in the BUI ratios (BUI after instillation/before instillation) at any point during the 120 minute period after instillation. However, in the H 03 subgroup, the BUI ratio temporarily decreased to 0.650 one minute after H 03 instillation (p = 0.0038). D group: In the AT subgroup, the BUI ratio significantly increased to 1.568 five minutes after AT instillation (p = 0.0259), but began to decrease 15 minutes after instillation and returned to the initial value 30 minutes after instillation. In the H 01 subgroup, the BUI ratio significantly increased to 1.531 five minutes after H 01 instillation (p = 0.0087), and was maintained at 1.347 120 minutes after instillation (p = 0.0088). In the H 03 subgroup, the BUI ratio rose to 1.544 15 minutes after H 03 instillation (p = 0.0009), and was maintained at high levels of 1.413 30 minutes after (p = 0.0122), 1.629 60 minutes after (p = 0.0008), and 1.407 120 minutes after instillation (p = 0.0008).

CONCLUSION: The current study confirms that both 0.1 and 0.3% sodium hyaluronate solution effectively improve tear film stability in dry eyes for up to two hours after instillation.

Nippon Ganka Gakkai Zasshi. 2011 Feb;115(2):134-41.
Yamaguchi M, Kutsuna M, Maruo H, Hara Y, Uno T, Kataoka H, Ohashi Y.
Department of Ophthalmology, Ehime Prefectural Central Hospital, Japan. masahiko@m.ehime-u.ac.jp

Abstract: What is different about our meibum?

Human Meibum Lipid Conformation and Thermodynamic Changes With Meibomian-Gland Dysfunction.

Purpose: Instability of the tear film with rapid tear break-up time is a common feature of aqueous deficient and evaporative dry eye diseases, suggesting there may be a shared structural abnormality of the tear film that is responsible for the instability. A change in the normal meibum lipid composition and conformation is possibly this event. Principle Component Analysis of infrared spectra of human meibum indicate that human meibum collected from normal donors (Mn) is more ordered than meibum from donors with meibomian gland dysfunction (Md). In this study we quantified the conformation of Md to test this finding.

Methods: Changes in lipid conformation with temperature were measured using infrared spectroscopy. There were two phases to our study. In phase 1 we measured the phase transitions of human samples, Mn and Md. In phase 2, we measured phase transitions of model lipid standards composed of different waxes and cholesterol ester.

Results: The phase transition temperature was significantly higher by 4°C for Md compared to Mn of age-matched donors with no history of dry-eye symptoms. Most (82%) of the phase-transition temperatures measured for Md were above the values for Mn. The small change in the transition temperature was amplified in the average lipid order (stiffness) at 33.4(o)C. The average lipid order at 33.4(o)C for Md was significantly higher (30%, p = 0.004), than for Mn. The strength of lipid-lipid interactions was 72% higher for Md compared to Mn. The ability of one lipid to influence the melting of adjacent lipids is termed cooperativity. There was no significant differences between Mn and Md in the phase transition cooperativity. Nor was there a difference between Mn and Md in the minimum order or maximum order that Mn and Md can achieve at very low and very high temperatures, respectively. From our model wax studies, we found that the phase transition of complex mixtures of natural lipids is 'set' by the level of unsaturation. A double bond decreased the phase transition temperature by about 40 °C. The addition of a second CH=CH moiety decreased the phase transition temperature by about 19 °C. Unsaturated waxes were miscible with saturated waxes. When a saturated wax was mixed with an unsaturated one, the saturated wax disproportionately increased the phase transition of the mixture by about 30 °C compared to the saturated wax alone. Cholesterol ester had little affect on the phase transition temperature of waxes. Model studies indicate that changes in the amount of lipid saturation rather than the amount of cholesterol esters could be a factor in the observed conformational changes.

Concluisions: Meibum lipid compositional changes with meibomian gland dysfunction reflect changes in hydrocarbon chain conformation and lipid-lipid interaction strength. Spectroscopic techniques are useful to study the lipid-lipid interactions and conformation of lipid from individual patients.

Invest Ophthalmol Vis Sci. 2011 Mar 11. [Epub ahead of print]
Borchman D, Foulks GN, Yappert MC, Bell J, Wells E, Neravetla S, Greenstone V.
Department of Ophthalmology and Visual Sciences, University of Louisville, 301 E. Muhammad Ali Blvd., Louisville, KY 40202, US;

Abstract: Epiphora in salivary gland transplantation

Proteomic Analysis of Human Transplanted Submandibular Gland in Patients with Epiphora after Transplantation.

Submandibular gland autotransplantation is effective for treating severe dry eye syndrome. However, more than 40% of patients show epiphora within 3 to 6 months after treatment. The mechanism underlying the hypersecretion in epiphora remains to be elucidated for developing novel interventions. Since salivary gland secretion is dependent on a variety of proteins, we analyzed the changes in protein expression in transplanted glands of epiphora patients with 2-D gel electrophoresis and electrospray ionization quadrupole/time-of-flight mass spectrometry and evaluated their possible roles in epiphora. There were 23 proteins showed altered expression in the glands of epiphora patients, 15 being up-expressed and 8 down-expressed. The expression of secretory proteins was decreased in these glands, including alpha-amylase, cystatin S, SA, and SN. In contrast, cytoskeletal proteins were all upregulated, including actin and vimentin. Immunofluorescence revealed the intensity ratio of F-actin in apical and lateral cytoplasm to total F-actin in acini was decreased in the glands of epiphora patients. Carbachol stimulation induced a similar redistribution of F-actin in the control glands. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was increased in both carbachol-stimulated and epiphora glands. Preincubation of submandibular glands with ERK1/2 inhibitors PD98059 or U0126 inhibited carbachol-induced F-actin redistribution. These results indicated that differentially expressed proteins participated in hypersecretion of transplanted submandibular glands, and the redistribution of F-actin might be involved in this hypersecretion in an ERK1/2-dependent manner

J Proteome Res. 2011 Mar 8. [Epub ahead of print]
Ding C, Zhang Y, Peng X, Wang Y, Zhang L, Cong X, Ding QW, Xiang RL, Wu LL, Yu GY.

Monday, March 21, 2011

Abstract: Corneal perforation in GVHD

Four cases of corneal perforation in patients with chronic graft-versus-host disease.
PURPOSE: To report the clinical features and investigate the underlying pathological processes of spontaneous corneal perforation in patients with ocular chronic graft-versus-host disease (cGVHD).
METHODS: A full ophthalmological evaluation of corneal perforation in four patients with cGVHD was performed. Three of them underwent deep anterior lamellar keratoplasty and samples from two of three patients were used for histopathological analyses.
RESULTS: Three patients were successfully treated by corneal transplantation. One patient was treated with a therapeutic soft contact lens, and the wound healed within 2 days. The common clinical features of these patients were (1) the presence of definite dry eye related to cGVHD in 3 of 4 patients and probable dry eye in one patient, (2) a central or paracentral site of corneal ulceration and perforation, with no sign of infection, and (3) prior use of a topical or systemic corticosteroid, and/or topical non-steroidal anti-inflammatory drugs. Immunohistochemical findings revealed an increased number of cluster of differentiation 68(+) (CD68(+)) macrophages and matrix metalloproteinase 9 (MMP-9) expression in the tissue surrounding the perforation.
CONCLUSIONS: Our report extends current information on the clinical features and pathological processes of corneal perforation in cGVHD by showing increased MMP-9 expression and the accumulation of CD68(+) positive macrophages in the affected areas.

Mol Vis. 2011 Feb 25;17:598-606.
Inagaki E, Ogawa Y, Matsumoto Y, Kawakita T, Shimmura S, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

Abstract: GVHD vs Sjogrens vs MGD

Tear physiology in dry eye associated with chronic GVHD.

The purpose of this study was to compare tear physiology characteristics of chronic GVHD (cGVHD)-associated dry eye to dry eye caused by Sjogren's syndrome (SS), a extreme form of aqueous-deficient dry eye, and meibomian gland dysfunction (MGD), the major cause of evaporative dry eye.

Tear turnover rate, evaporation and osmolarity along with meibomian gland dropout and lipid layer interferometric patterns were assessed in the right eyes of 12 patients with dry eye associated with cGVHD, 12 age-matched patients with SS and 12 age-sex matched subjects with MGD.

In cGVHD, the decrease in tear turnover rate was similar (P=0.33), but the number of non-functioning meibomian glands was significantly higher (P<0.01) than in SS. Tear evaporation rate in cGVHD dry eye was found to be similar to that in MGD (P=0.36) and significantly higher than in SS (P<0.01). The lipid layer was most unstable in cGVHD compared with other groups. There was no variation in tear volume across all groups. Although statistical significance was not detected, the mean tear osmolarity (333.51±14.67mOsm/L) was highest in cGVHD.

Major aspects of tear physiology were severely impaired in cGVHD-associated dry eye

Bone Marrow Transplant. 2011 Mar 7. [Epub ahead of print]
Khanal S, Tomlinson A.
School of Natural Sciences, University of Western Sydney, Sydney, Australia.

New gizmo: Blink Now

We've come a long way from those little computer-shaped stress balls I used to get printed up that said "Blink now!", huh?

Now, there's a ~$75 gadget to place by your computer which will remind you more effectively. Check out the new "Blink Now" (press release below) sold in the UK. Funny how the computer gaming industry is one of the newer forces currently driving innovation of a few new things for dry eye, such as Gunnar Optiks' line of computer glasses. Hopefully their role in the market will lead to more and more dry eye tools for the younger generations. We need all the help we can get....

Blink Now – prevent headache, dry eye, migraine and eye strain – just by blinking!

Doncaster, UK - 10/03/2010

Blink Now is the only device which works to pro-actively prevent headaches, dry eyes, tired eyes and migraines (as a result of Computer Vision Syndrome). Computer Vision Syndrome is a problem which over 90% of computer user’s suffer from (excessive usage is classed as anything over 3 hours per day). You may not even realise that your headaches, dry eyes and migraines are being caused by your computer screen and this is why the increasing awareness of CVS is prompting people to now try to prevent it.

Computer Vision Syndrome?

CVS (Computer Vision Syndrome) symptoms are headaches, dry eyes, migraines, screen fatigue and computer eye strain - it is often un-diagnosed as users don’t realise that the symptoms are a direct result of using their computer screens for excessive amounts of time (anything over 3 hours).

Medical studies have proven one of the key contributing factors to CVS is a lack of blinking – when you don’t blink, your eyes don’t produce tears (which act as a natural lubricant) - dry eyes lead to headaches and as a result Blink Now was specially designed to help prevent this.

You may be asking yourself “why are people forgetting to blink” but when you understand more about CVS it becomes apparent that, it isn’t a case of “forgetting” to blink, but more a case of “forcing” your eyes to stay open (while you are focusing on your screen). Blink Now sits on top of your screen and sub-consciously prompts you to blink – it is very a simple solution, but very effective.

The Blink Now device is the size of a webcam and is compatible with both PC and MAC (and any other device with a powered USB port) and requires no setup – just plug it in and switch it on!

Blink Now is available now at http://www.blazeeurope.com at only £49.99

Please visit the link below for more information:


Information about all Blaze products can be found at http://www.blazeeurope.com

The latest news from Blaze can be found here: http://www.blazeeurope.com/news

Further information about Blink Now can be found at: http://www.blinknow.co.uk/