Clinical Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

Purpose: To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil). Methods: Sixteen eyes of 8 patients with Sjogren syndrome dry eyes (age, 51.13 +/- 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops. Results: The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops. Conclusions: Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.

Spontaneous Interblink Time Distributions in Patients with Graves` Orbitopathy and Normal Subjects

PURPOSE. To determine the shape of spontaneous interblink time interval distributions obtained in a long observation period in normal subjects and patients with Graves` orbitopathy. METHODS. The magnetic search coil technique was used to register the spontaneous blinking activity during 1 hour of video observation of two groups of 10 subjects each (normal controls aged 27-61 years, mean +/- SD = 46.0 +/- 13.6; patients with Graves` orbitopathy aged 33-61 years, mean +/- SD +/- 46.7 +/- 8.9). The spontaneous blink rate of each subject was calculated for the entire period of observation and for 56 five-minute bins. Histograms of the interblink time interval were plotted for each measurement of blink rate. RESULTS. Neither the overall mean blink rate (controls, 19.8 +/- 4.9; Graves`, 17.6 +/- 5.4) nor the interblink time (controls, 5.2 +/- 3.1, Graves`, 7.9 +/- 3.5) differed between the two groups. There was a large variation of both measurements when the 5-minute bins were considered. The interblink time distribution of all subjects was highly positively skewed when the 1-hour period was measured. A significant number of the 5-minute bin distributions deviated from the overall pattern and became symmetric. CONCLUSIONS. The normal blinking process is characterized by highly positively skewed interblink time distributions. This result means that most blinks have a short time interval, and occasionally a small number of blinks have long time intervals. The different patterns of distribution described in the early literature probably represent artifacts because of the small samples analyzed. (Invest Ophthalmol Vis Sci. 2011;52:3419-3424) DOI:10.1167/iovs.10-7060

Lighting conditions at an operating room in a Portuguese maternity

Lighting is one of the most important factors in human interaction with the environment. Poor lighting may increase the risk of accidents and could also cause a variety of symptoms including: rapid fatigue, headaches, eyestrain, tired eyes, dry eyes, ocular surface symptoms (watery and irritated eyes), decreased concentration and stress. Specific disorders: degeneration of the sharpness of vision (blurred and double vision) and slowness in changing focus. Apart from the advantages in the health and welfare for the workers, good lighting also leads to better job performance (faster), less errors, better safety, fewer accidents and less absenteeism. The overall effect is: better productivity. Good lighting includes quantity and quality requirements, and should necessarily be appropriate to the activity/task being carried out, bearing in mind the comfort and visual efficiency of the worker.

Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation.

The TNF family ligand ectodysplasin A (EDA) regulates the induction, morphogenesis and/or maintenance of skin-derived structures such as teeth, hair, sweat glands and several other glands. Deficiencies in the EDA - EDA receptor (EDAR) signalling pathway cause hypohidrotic ectodermal dysplasia (HED). This syndrome is characterized by the absence or malformation of several skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes, susceptibility to airways infections and crusting of various secretions. The EDA-EDAR system is an important effector of canonical Wnt signalling in developing skin appendages. It functions by stimulating NF-κB-mediated transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH), fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ) pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. In animal models of Eda-deficiency, soluble EDAR agonists can precisely correct clinically relevant symptoms with low side effects even at high agonist doses, indicating that efficient negative feedback signals occur in treated tissues. Hijacking of the placental antibody transport system can help deliver active molecules to developing foetuses in a timely manner. EDAR agonists may serve to treat certain forms of ectodermal dysplasia.

The retina in Parkinson's disease

As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of ‘higher’ (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

Enhanced-depth optical coherence tomography for imaging horizontal rectus muscles in Graves' orbitopathy.

PURPOSE Graves' orbitopathy (GO) is an extraocular eye disease with symptoms ranging from minor discomfort from dry eyes to strabismus and visual loss. One of the hallmarks of active GO is visible hyperemia at the insertion of the extraocular muscles. The aim of the present study was to evaluate the use of enhanced-depth imaging spectral domain anterior segment optical coherence tomography (EDI SD AS-OCT) for detecting pathological changes in horizontal recti muscles of patients with GO. METHODS Prospective cross sectional study of 27 eyes. Only women were included. EDI AS-OCT was used to measure the thickness of the tendons of the horizontal recti muscles in a predefined area in patients with GO and healthy controls. RESULTS EDI AS-OCT was able to image the tendons of the horizontal recti muscles in both healthy controls and patients suffering from GO. The mean thickness of the medial rectus muscle (MR) tendon was 256.4 μm [±17.13 μm standard deviation (SD)] in the GO group and, therefore, significantly thicker (p = 0.046) than in the healthy group which had a mean thickness of 214.7 μm (±5.516 μm SD). There was no significant difference in the mean thickness of the tendon of the lateral recti muscles (LRs) between these groups. CONCLUSION This is the first report showing that EDI AS-OCT is suitable to detect swelling at the insertion site of the MR muscle in GO. MR tendon thickness may be a useful parameter to monitor activity in these patients.

Editorial

The year so far has been a slow start for many businesses, but at least we have not seen the collapse of as many businesses that we were seeing around two years ago. We are, however, still well and truly in the midst of a global recession. Interest rates are still at an all time low, UK house prices seem to be showing little signs of increase (except in London where everyone still seems to want to live!) and for the ardent shopper there are bargains to be had everywhere. It seems strange that prices on the high street do not seem to have increased in over ten years. Mobile phones, DVD players even furniture seems to be cheaper than they used to be. Whist much of this is down to cheaper manufacturing and the rest could probably be explained by competition within the market place. Does this mean that quality suffered too? Now that we live in a world when if a television is not working it is thrown away and replaced. There was a time when you would take it to some odd looking man that your father would know who could fix it for you. (I remember our local television fix-it man, with his thick rimmed bifocal spectacles and a poor comb-over; he had cardboard boxes full of resistors and electrical wires on the floor of his front room that smelt of soldering irons!) Is this consumerism at an extreme or has this move to disposability made us a better society? Before you think these are just ramblings there is a point to this. According to latest global figures of contact lens sales the vast majority of contact lenses fitted around the world are daily, fortnightly or monthly disposable hydrogel lenses. Certainly in the UK over 90% of lenses are disposable (with daily disposables being the most popular, having a market share of over 50%). This begs the question – is this a good thing? Maybe more importantly, do our patients benefit? I think it is worth reminding ourselves why we went down the disposability route with contact lenses in the first place, and unlike electrical goods it was not just so we did not have to take them for repair! There are the obvious advantages of overcoming problems of breakage and tearing of lenses and the lens deterioration with age. The lenses are less likely to be contaminated and the disinfection is either easier or not required at all (in the case of daily disposable lenses). Probably the landmark paper in the field was the work more commonly known as the ‘Gothenburg Study’. The paper, entitled ‘Strategies for minimizing the Ocular Effects of Extended Contact Lens Wear’ published in the American Journal of Optometry in 1987 (volume 64, pages 781-789) by Holden, B.A., Swarbrick, H.A., Sweeney, D.F., Ho, A., Efron, N., Vannas, A., Nilsson, K.T. They suggested that contact lens induced ocular effects were minimised by: •More frequently removed contact lenses •More regularly replaced contact lenses •A lens that was more mobile on the eye (to allow better removal of debris) •Better flow of oxygen through the lens All of these issues seem to be solved with disposability, except the oxygen issue which has been solved with the advent of silicone hydrogel materials. Newer issues have arisen and most can be solved in practice by the eye care practitioner. The emphasis now seems to be on making lenses more comfortable. The problems of contact lens related dry eyes symptoms seem to be ever present and maybe this would explain why in the UK we have a pretty constant contact lens wearing population of just over three million but every year we have over a million dropouts! That means we must be attracting a million new wearers every year (well done to the marketing departments!) but we are also losing a million wearers every year. We certainly are not losing them all to the refractive surgery clinics. We know that almost anyone can now wear a contact lens and we know that some lenses will solve problems of sharper vision, some will aid comfort, and some will be useful for patients with dry eyes. So if we still have so many dropouts then we must be doing something wrong! I think the take home message has to be ‘must try harder’! I must end with an apology for two errors in my editorial of issue 1 earlier this year. Firstly there was a typo in the first sentence; I meant to state that it was 40 years not 30 years since the first commercial soft lens was available in the UK. The second error was one that I was unaware of until colleagues Geoff Wilson (Birmingham, UK) and Tim Bowden (London, UK) wrote to me to explain that soft lenses were actually available in the UK before 1971 (please see their ‘Letters to the Editor’ in this issue). I am grateful to both of them for correcting the mistake.

International flavours

It is an Olympic year and we have just witnessed the fantastic games hosted by Rio de Janeiro. Well done to team USA for winning the most medals overall but also well done to so many other nations and individuals who performed so well or were ambassadors in other ways. Teenage swimmer Yusra Mardini who swam for the refugee team and South Africa's Wayde van Niekerk who broke the longstanding 400 m record of Michael Johnson that has stood since 1999. Of course, we must mention sprinter Usain Bolt and swimmer Michael Phelps, who have now transcended superstar status and entered a new level of icon. My personal highlight was the sportsmanship witnessed in the 5000 m when American Abbey D’Agostino was accidentally felled by New Zealand runner Nikki Hamblin. D’Agostino helped Hamblin back to her feet but slumped to the track after realising her own injury. Hamblin helped her up and stayed with her so that both completed the race. The International Olympic Committee has awarded both with the prestigious Pierre de Coubertin award, also known as the International Fair Play Trophy. Fair play is of paramount importance in publishing in peer-reviewed papers. At CLAE we try and maintain, as do other journals, this by ensuring double blind peer review and allowing authors to select the most appropriate handling editor for their submission. Our handling editors are placed across the world (2 in Europe, 1 in the Americas, 1 in Australia and 1 in Asia) and part of their role is to encourage submissions from their region. Over the last decade we certainly have seen more and more papers from places that haven’t previously published in CLAE. In this issue of CLAE we have a true international blend of papers. We have papers from authors from the UK, USA, Iran, Jordan, France, Poland, Turkey, Nigeria, France, Spain and Brazil. I think it's a testament to the continued success of the journal that we are attracting new writers from so many parts of the world and retain papers from more established authors and research centres. We do continue to attract many weaker papers that are rejected early in the review process. Often these will be unexceptional case reports or papers describing a surgical technique. Case reports are published but only those that offer something original and especially those with interesting photographs. In this issue you will see Professor James Wolffsohn (UK) has an interesting paper around a lot of the focus of his recent research activity into clinical evaluation of methods of correcting presbyopia. In this paper he highlights predictors to aid success of presbyopic contact lenses. If you have been involved in any clinical work or research in the field of dry eye disease then you will know well the CLDEQ (Contact Lens Dry Eye Questionnaire) devised by Robin Chalmers and her colleagues (USA). This issue of CLAE details the latest research using the CLDEQ-8 (the 8 item version of the CLDEQ). The Shahroud Eye Cohort Study has produced many papers already and in this issue we see Fotouhi Akbar (Iran) looking at changes in central and peripheral corneal thickness over a five year period. These days we use a lot of new instrumentation, such as optical low-coherence reflectometry. In this issue Emre Güler (Turkey) compares that to a new optical biometry unit. Dry eye is more common and in this issue we see a study by Oluyemi Fasina (Nigeria) to investigate the disease in adults in South-West Nigeria. The TearLab™ is now commonly used to investigate osmolarity and Dorota Szczesna-Iskander (Poland) looks at measurement variability of this device. Following the theme of dry eyes and tear testing Renaud Laballe (France) looks at the use of scleral lenses as a reservoir-based ocular therapeutic system. In this issue we have a couple of papers looking at different aspects of keratoconus. Magdalena Popiela (UK) looks at demographics of older keratoconic patients in Wales, Faik Orucoglu (Turkey) reports a novel scoring system for distinguishing keratoconus from normal eyes, Gonzalo Carracedo (Spain) reports the effect of rigid gas permeable lens wear on dry eye in keratoconus and Hatice Nur Colak (Turkey) compares topographic and aberrations in keratoconus. Other interesting papers you will find are Mera Haddad (Jordan) investigates contact lens prescribing in Jordan, Camilla Fraga Amaral (Brazil) offers a report on the use of ocular prosthetics, Naveed Ahmed Khan (Malaysia) reports of the use of dimethyl sulfoxide in contact lens disinfectant and Michael Killpartrick (UK) offers a short piece with some useful advice on contamination risk factors that may occur from the posterior surface of disposable lenses. So for this issue I would say that the Gold Medal for biggest contribution in terms of papers has to go to Turkey. I could have awarded it to the UK too, but Turkey has three full papers and the UK has two plus one short communication. Turkey is also one of the countries that has shown the largest increase in submissions over the last decade. Finally, welcome aboard to our newest Editorial Board Member Nicole Carnt from Australia. Nicole has been an active researcher for many years and acted as a reviewer for CLAE many times in the past. We look forward to working with you.

Two-Year Outcome of Partial Lacrimal Punctal Occlusion in the Management of Dry Eye Related to Sjogren Syndrome

Purpose: To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjogren syndrome. Material and Methods: Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 +/- 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate. Results: The average lacrimal punctum diameter before the procedure was 0.65 +/- 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion. Conclusion: Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjogren syndrome.

New approaches and potential treatments for dry age-related macular degeneration

Emerging treatments for dry age-related macular degeneration (AMD) and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

Clinical Characterization of Asymptomatic or Minimally Symptomatic Young Patients Showing Signs Compatible With Dry Eye: A Pilot Study

Purpose: To evaluate and characterize the clinical profile of young asymptomatic or minimally symptomatic patients without diagnosis of dry eye but showing signs compatible with dry eye syndrome (DES). Methods: Prospective study including a total of 50 consecutive subjects with ages ranging from 18 to 40 years that were identified as asymptomatic or minimally symptomatic by means of the Ocular Surface Disease Index (OSDI) (score of <22). In all patients, a complete battery of tests for the diagnosis of DES was performed including the evaluation of the tear film break-up time (TFBUT), the level of corneal and conjunctival staining, and the eyelid and Meibomian morphology. Results: The OSDI score was significantly higher in women than in men (median: 12.5 vs. 5.3, P=0.01). Low grades of ocular surface staining, dysfunction of Meibomian gland expression, and alteration of quality of Meibomian secretions were observed in 56%, 58%, and 84% of eyes, respectively. More eyes with some dysfunction of Meibomian gland expressibility had a TFBUT less than 5 sec (P=0.033). A statistically significant difference in the OSDI score was found between patients with and without systemic allergies (P=0.036) and between male and female (P=0.01). Likewise, the OSDI score was significantly higher in those women wearing contact lenses compared with those not wearing them (P=0.012). Conclusions: Asymptomatic or minimally symptomatic young subjects may present low grades of clinical signs compatible with DES, with a trend to more symptomatology in women and allergic patients. These outcomes should be confirmed in future studies with larger samples.

Randomised masked clinical trial of the MGDRx eyebag for the treatment of meibomian gland dysfunction-related evaporative dry eye

Background/aims To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. Methods Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, noninvasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. Results Differences between test and control eyes at baseline were not statistically signi ficant for all measurements ( p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes ( p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months ( p<0.05), although the bene fit was greater in those who continued usage 1-8 times a month (p<0.001). Conclusions The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. Trial registration number NCT01870180.