Report of the inaugural meeting of the TFOS i2 = initiating innovation Series:targeting the unmet need for dry eye treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

What is the optimum artificial treament for dry eye?

Dry eye disease is a common clinical condition whose aetiology and management challenges clinicians and researchers alike. Practitioners have a number of dry eye tests available to clinically assess dry eye disease, in order to treat their patients effectively and successfully. This thesis set out to determine the most relevant and successful key tests for dry eye disease diagnosis/ management. There has been very little research on determining the most effective treatment options for these patients; therefore a randomised controlled study was conducted in order to see how different artificial treatments perform compared to each other, whether the preferred treatment could have been predicted from their ocular clinical assessment, and if the preferred treatment subjectively related to the greatest improvement in ocular physiology and tear film stability. This research has found: 1. From the plethora of ocular the tear tests available to utilise in clinical practice, the tear stability tests as measured by the non-invasive tear break (NITBUT) up time and invasive tear break up time (NaFL TBUT) are strongly correlated. The tear volume tests are also related as measured by the phenol red thread (PRT) and tear meniscus height (TMH). Lid Parallel Conjunctival Folds (LIPCOF) and conjunctival staining are significantly correlated to one another. Symptomology and osmolarity were also found to be important tests in order to assess for dry eye. 2. Artificial tear supplements do work for ocular comfort, as well as the ocular surface as observed by conjunctival staining and the reduction LIPCOF. There is no strong evidence of one type of artificial tear supplement being more effective than others, and the data suggest that these improvements are more due to the time than the specific drops. 3. When trying to predict patient preference for artificial tears from baseline measurements, the individual category of artificial tear supplements appeared to have an improvement in at least 1 tear metric. Undoubtedly, from the study the patients preferred artificial tear supplements’ were rated much higher than the other three drops used in the study and their subjective responses were statistically significant than the signs. 4. Patients are also willing to pay for a community dry eye service in their area of £17. In conclusion, the dry eye tests conducted in the study correlate with one another and with the symptoms reported by the patient. Artificial tears do make a difference objectively as well as subjectively. There is no optimum artificial treatment for dry eye, however regular consistent use of artificial eye drops will improve the ocular surface.

Essential fatty acids for dry eye:a review

Purpose Dry eye is a common complaint often encountered in optometric practice. However, it is a difficult condition to treat as clinical signs do not always correlate with patient symptoms. Essential fatty acids (EFA), particularly omega-3 EFA, may be effective in dealing with the underlying causes. Methods A literature review was carried out on the PubMed, ScienceDirect and Ovid databases. Searches included keywords such as ‘dry eye’, ‘essential fatty acids’ and ‘nutrition’ to find articles relating to the treatment of dry eye syndrome (DES) with omega-3 EFAs. Results Omega-3 and -6 EFAs need to be consumed together within a reasonable ratio to be effective. Currently, typical diets in developed countries lack omega-3 EFA and this results in an overexposure to omega-6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti-inflammatory action in the lacrimal gland preventing apoptosis of the secretory epithelial cells. Supplementation clears meibomitis, allowing a thinner, more elastic lipid layer to protect the tear film and cornea. Conclusion Dietary supplementation of omega-3 EFA has already proven to be effective in coronary heart disease and arthritis. Safety is not a concern as it works synergistically with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA may be beneficial in the treatment and prevention of DES.

Screening for eye disease in the elderly:is it worth it?

Should we be screening for eye disorders in the elderly population? Visual impairment in the elderly can be associated with reduced functional status and quality of life, low social contact, depression, and falls and hip fractures (Dargent-Molina et al, 1996). It therefore would seem sensible to identify those elderly patients who have or are at risk of developing sight-threatening eye disorders, and offer them treatment. However, screening for disease of any kind raises a number of issues.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

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.

Management of allergic conjunctivitis and dry eye

Ocular allergy is a common eye condition encountered in clinical practice. However, little is known how seasonal allergic conjunctivitis (SAC), the most common subtype, is managed in clinical practice. Further, dry eye, another common eye condition, may be misdiagnosed as SAC and vice-versa as they share similar signs and symptoms. In addition, despite the frequent recommendation of non-pharmacological treatments for SAC, evidenceto support their use has not been identified in the scientific literature. The aim of this thesis was therefore to determine the actual diagnosis and management of SAC and dry eye in clinical practice and investigate the efficacy of non-pharmacological treatments for these conditions. The diagnostic and management strategies for SAC and dry eye employed by pharmacy staff are found to be inconsistent with current guidelines and scientific evidence based upon a mystery shopper design. Cluster analysis of tear film metrics in normal and dry eye patients identified several clinically relevant groups of patients that may allow for targeted treatment recommendations. Using a novel environmental chamber model of SAC, the use of artificial tears and cold compresses, either alone or combined is an effective treatment modality for acute and symptomatic SAC, on a par with topical anti-allergic medication, and has been demonstrated for the first time. In addition, eyelid warming therapy with a simple, readily available, seed filled device is an effective method of treating meibomian gland dysfunction (MGD) related evaporative dry eye, perhaps the most common dry eye subtype. A greater focus on ophthalmology must be implemented as part of the formal education and training of pharmacy staff, while greater professional communication between community pharmacists, optometrists and the population they serve is required. Artificial tears and cold compresses may be considered as front line agents for acute SAC by pharmacy staff and optometrists, to whom pharmacological treatment options are limited.

Does cardiovascular therapy affect the onset and recurrence of preretinal and vitreous haemorrhage in diabetic eye disease?

Aims To review the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous haemorrhage in diabetic patients. Methods Retrospective case note analysis of diabetic patients with vitreous haemorrhage from the Diabetic Eye Clinic at Birmingham Heartlands Hospital. Results In total, 54 patients (mean age 57.1, 37 males, 20 type I vs34 type II diabetic patients) were included. The mean (SD) duration of diagnosed diabetes at first vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and 14.8 (9.3) years for type II diabetic patients (P<0.01, unpaired t-test, two-tailed). Aspirin administration was not associated with a significantly later onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous haemorrhage: 21.4 years until vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P=0.09, two-tailed, unpaired t-test, not statistically significant). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post haemorrhage was 1067 (77–3842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolaemia, and macrovascular complications were not associated with a significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor decrease the 1-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence (Fisher exact P<0.05; two-tailed) with an odds ratio (95% CI) of 0.25 (0.1–0.95). Conclusion In this retrospective analysis, the onset of preretinal/vitreous haemorrhage was not found to be accelerated by gender, hypertension, hypercholesterolaemia, evidence of macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration accelerated the onset or recurrence of first vitreous haemorrhage. Statins may have a protective role, both delaying and reducing the recurrence of haemorrhage.

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications. © 2014 The Author.

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.

Management of dry eye in UK pharmacies

Purpose - To investigate the ability of pharmacy staff in the United Kingdom (UK) to diagnose and treat dry eye. Methods - A mystery shopper technique to simulate a patient with presumed dry eye was used in 50 pharmacy practices in major towns and cities across the UK. Pharmacies were unaware of their involvement in the study. With the exception of a predetermined opening statement to initiate the consultation, no further information was volunteered. Questions asked, diagnoses given, management strategy advised and staff type was recorded immediately after the consultation. Results - The mean number of questions was 4.5 (SD 1.7; range 1–10). The most common question was the duration of symptoms (56%) and the least common was whether the patient had a history of headaches (2%). All pharmacy staff gave a diagnosis, but the majority were incorrect (58%), with only 42% correctly identifying dry eye. Treatment was advised by 92% of pharmacy staff, with the remaining 8% advising referral directly to the patient's GP or optometrist. Dry eye treatments involved topical ocular lubrication via eye drops (90%) and lipid based sprays (10%). However, only 10% gave administration advice, 10% gave dosage advice, 9% asked about contact lens wear, and none offered follow up although 15% also advised GP or optometrist referral. Conclusions - There is a need for improved ophthalmological training amongst pharmacists and pharmacy staff and establishment of cross referral relationships between pharmacies and optometry practices.

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.

The microbiology of the eye

Infection of the external structures of the eye is one of the commonest types of eye disease worldwide. In addition, although relatively impermeable to microorganisms, infection within the eye can result from trauma, surgery or systemic disease. This article reviews the general biology of viruses, bacteria, fungi and protozoa and the major ocular infections that they cause. In addition, the effectiveness of the various antimicrobial agents in controlling ocular disease is discussed. Because of changes in the normal ocular flora, continuous monitoring of the microbiology of the eye will continue to be important in predicting future types of eye infection. Basic research is also needed into the interactions of microbes at the ocular surface. There is increasing microbial resistance to the antimicrobial agents used to treat ocular infections and hence, new antimicrobial agents will continue to be needed together with new methods of drug delivery to increase the effectiveness of existing antimicrobial agents.