TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

The Impact of Probiotics and Prebiotics on Dry Eye Disease Signs and Symptoms.

Dry eye is considered an inflammatory disease. Gut microbiota are important in the regulation of low-grade chronic inflammation, including in the eye. Probiotics and prebiotics are increasingly used to regulate chronic-disease-associated gut dysbiosis. Therefore, this double-masked, randomized controlled clinical trial aimed to explore the potential of oral probiotics and prebiotics in the management of dry eye disease. In total, 41 participants with dry eye received probiotic and prebiotic supplements (treatment group, n = 23) or respective placebos (control group, n = 18) for 4 months. Dry eye symptoms and signs were evaluated using the Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire 5, osmolarity, non-invasive keratograph break-up time (NIKBUT), ocular surface staining, tear meniscus height (TMH), lipid layer thickness, and conjunctival redness. After 4 months, the average OSDI score of the treatment group was significantly better compared to that of the controls (16.8 ± 5.9 vs. 23.4 ± 7.4; p < 0.001). The NIKBUT and TMH did not change significantly with treatment (p = 0.31 and p = 0.84) but reduced significantly for controls on average by −5.5 ± 1.0 secs (p = 0.03) and 0.2 ± 0.1 mm (p = 0.02). These data suggest that probiotics and prebiotics might be effective in the management of dry eye disease.

The validity of point of care tear film osmometers in the diagnosis of dry eye.

PURPOSE: To determine the repeatability of TearLab and I-PEN osmometers in vivo and their accuracy in vitro. DESIGN: Prospective, single-visit study. METHODS: The tear osmolarity of 28 participants was evaluated with TearLab and I-PEN on two occasions in random order, over a 2-h period. Both eyes were measured in a randomised order. Coefficients of repeatability (CoR) were determined for each device, together with the bias and limits of agreement between them. For the in vitro experiment, the osmolarity was measured by both osmometers in five solutions (290, 297, 342, 338 and 383 mOsm/L) at two different temperatures (22 and 37°C) with a total of four consecutive measures. RESULTS: The CoRs for the TearLab and I-PEN in the right and left eyes were 26.2, 21.3, 33.6 and 28.3 mOsm/L, respectively. Across the first and second repeats, TearLab showed consistency of diagnosis for 50% of participants with 29% as dry eye positive, while I-PEN indicated 68% consistency of diagnosis with 57% dry eye positive. The instruments agreed on the diagnosis in 46.5% of cases. In vitro comparison showed that the average measurement errors for TearLab and I-PEN were -10 ± 13 and 31 ± 39 mOsm/L at 22°C, and 4 ± 13 and 20 ± 51 mOsm/L at 37°C. CONCLUSIONS: In vitro, both instruments showed reasonable accuracy and repeatability at mid-range osmolarities, but repeatability generally declined at higher and lower levels. While TearLab accuracy remained consistent across the osmolarity range, measurement errors for I-PEN noticeably increased outside the mid-range. In vivo, both instruments displayed poor repeatability. This casts doubt on the value of utilising either instrument to establish osmolarity as a factor in the diagnosis of dry-eye, according to currently recommended diagnostic guidelines (TFOS DEWS II), if only a single measurement is taken from each eye.

Dry eye disease: an (in)convenient truth.

The salient rise of chronic disease from the mid-twentieth century threatens to overwhelm public health systems in an increasing number of countries and is now considered an epidemic. Dry eye disease is an underappreciated disorder that bears all the hallmarks of chronic disease. Preventative health care seeks improved and sustainable patient engagement in the self-management of health to limit the progress and extent of chronic disease. Anthropogenic environments engendering lifestyles and behaviours that can be detrimental to human health, can be considered as direct or indirect threats to successful preventative health strategies. Chronic disease can be viewed as the result of physiological responses of the human body to the modern environment. The quest for an increasingly convenient, global, and disease-free lifestyle is ironically threatening to undo the gains in health and quality of life made over the last one hundred years. Considering dry eye disease as an anthropogenic chronic disease, contributions of diet (food and beverages consumed) and nutrition (extending to relationships with self, community, and nature) to development of dry eye disease are explored in this review. Evidence of environmental and behavioural instigators of chronic disease with an emphasis on production, disbursement, and preservation of food, is presented. Furthermore, evidence of traditional food practices that offer resistance to the development of chronic systemic inflammatory disorders are reviewed as an exemplar of potential strategies that can be put into practice by individuals and communities to reinstate a balanced life, community and planet.

Review: Myopia control strategies recommendations from the 2018 WHO/IAPB/BHVI Meeting on Myopia.

Myopia is a major public health problem, particularly in East Asia. In this summary report, we present key findings and recommendations on strategies for myopia control discussed during the meeting jointly organised by the WHO Regional Office for the Western Pacific, the International Agency for the Prevention of Blindness and the Brien Holden Vision Institute. First, myopia prevalence was reported to be increasing, with up to 80% of junior school students with myopia in East Asia. However, common challenges in implementing myopia control strategies on a national level included lack of school screening programme, and paucity of accurate prevalence data. Second, there continues to be broad public misconception about myopia and myopia control, including lack of parental awareness and resistance to wearing spectacles. Third, best practices for myopia management were shared, and recommendations for policy implementation are presented in this review. Key recommendations from this meeting include increased public education to raise parent and teacher awareness; encouragement of increased outdoor time of 2-3 hours per day for schoolchildren-as a practical public health intervention that has been shown to potentially reduce onset and progression of myopia. Governments and non-governmental organisations are encouraged to collaborate, especially education and health ministries to develop national myopia prevention programme. Lastly, it is important to emphasise that the key recommendations, such as increasing outdoor time for schoolchildren, are specific for East Asian nations in the Western Pacific region and may not be entirely applicable for Western nations.

The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?

Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated "Western life-style" diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.

The effect of Blephadex™ Eyelid Wipes on Demodex mites, ocular microbiota, bacterial lipase and comfort: a pilot study.

PURPOSE: To investigate the effect of Blephadex™ Eyelid Wipes on Demodex mites, ocular microbiota, bacterial lipase, tear film characteristics and ocular comfort after one month of daily use. METHODS: Twenty subjects were randomly assigned to use the Blephadex™ Eyelid Wipes on either eye once daily for 30 days whilst the contralateral eye was left untreated in this observer-masked, within-subject study. Demodex count, eyelid bacterial colony count, Tearscope Plus non-invasive tear break up time (NITBUT), Lipiview® tear film lipid layer thickness and phenol red thread test tear volume were measured at baseline and 30 days. Bacterial lipase was quantified from single bacterial colonies using a glycerol monolaurate assay. Ocular comfort was assessed at both visits using the Ocular Surface Disease Index (OSDI) questionnaire and visual analogue scales (VAS) to capture monocular symptoms of itching, dryness and overall discomfort. RESULTS: Six males and 14 females, median age 63.5 (range 48-76) completed the study. A statistically significant reduction in Demodex count was observed in treated eyes only (median ±â€¯IQR: treated eyes 2 ±â€¯3 vs. 0 ±â€¯2, ANOVA p = 0.04). Bacterial colony count, lipase production, NITBUT, lipid layer thickness and tear volume remained unchanged (p > 0.05). Overall comfort improved over time in treated eyes only (15 ±â€¯32 vs. 10 ±â€¯16, p = 0.05). Dryness symptoms significantly reduced in both treated and untreated eyes (23 ±â€¯42 vs. 12 ±â€¯21 and 23 ±â€¯41 vs. 10 ±â€¯15, p = 0.02). The OSDI and ocular itch scores remained unchanged (p > 0.05). CONCLUSION: In this pilot study, no changes were observed in ocular microbiota, tear film characteristics or bacterial lipase in eyes treated with Blephadex™ Eyelid Wipes after one month of daily use in this normal healthy population. Although a statistically significant reduction in Demodex count was observed in treated eyes, overall numbers of Demodex were low. A parallel group, placebo-controlled, randomised clinical trial in a population with active blepharitis is warranted to further elucidate these preliminary findings.

Simulation in Ophthalmic Training.

Vision impairment and blindness arise both as a cause, and a consequence, of poverty. Achievement of the United Nations Sustainable Development Goals in providing universal access and equity in eye care, both within and between among countries, remains challenging. A severe shortage of eye care providers is creating unnecessary blindness and vision impairment in developing communities worldwide. Education and training develops and strengthens the capacity of emerging nations to contribute to global eye health and the World Health Organization Development Goals in an effective and sustainable way. Although relative to other medical professions, adoption of simulation in ophthalmic training has been relatively slow, simulation potentially offers reduced training costs, increased accessibility, objective measurement of training outcomes, and improvements in patient safety during and after clinician training, all of which can help address the global burden of vision impairment and blindness. Simulation training offers advantages over apprenticeship models, the traditional mode of transferring knowledge and skills in medicine and health, which suffers from imperfect transference due to inherent biases, heuristic and idiosyncratic expectations of experts, and subjective measures of outcomes. Simulation does not completely do away with these confounders because it is made to fit into established curricula, making it difficult to measure effectiveness of the simulation in isolation. The power of simulation training for resource-limited regions and countries is immense in offering cost-effective training in-country; however, it is important that any such tools are developed within the context of the limitations in situ.

Genetic factors and molecular mechanisms in dry eye disease.

Dry eye disease (DED) is a complex condition with a multifactorial etiology that can be difficult to manage successfully. While external factors are modifiable, treatment success is limited if genetic factors contribute to the disease. The purpose of this review is to compile research describing normal and abnormal ocular surface function on a molecular level, appraise genetic studies involving DED or DED-associated diseases, and introduce the basic methods used for conducting genetic epidemiology studies.

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

OBJECTIVE: To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. METHODS: This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. RESULTS: Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). CONCLUSION: Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

The impact of diabetes on corneal nerve morphology and ocular surface integrity.

Diabetes mellitus is a chronic disease that results from inadequate insulin production or ineffective insulin utilization. It is one of the most common systemic diseases worldwide with increasing prevalence. Diabetes mellitus is associated with premature mortality, macrovascular complications such as cardiovascular disease, and microvascular complications, including nephropathy leading to kidney failure, potentially blinding diabetic retinopathy, and diabetic neuropathy. While the retinal complications of diabetes are well recognized by eye care professionals, the effects on the ocular surface are poorly understood. Recent studies have reported on the association between peripheral neuropathy and corneal neuropathy, showing the latter to be of predictive value for the systemic disease. Corneal neuropathy can lead to loss of corneal sensation and can ultimately result in neurotrophic ulcers and significant visual morbidity. The epithelial fragility and poor wound healing that result from reduced epithelial adhesion to the underlying basement membrane in diabetes, together with corneal neuropathy, are thought to increase the susceptibility to persistent corneal erosions and infection, as well as to increase the risk of post-surgical complications. The aim of this article is to review the impact of diabetes on corneal nerve morphology and ocular surface integrity. Changes in the tear film and ocular surface microbiome are highlighted in discussion of the mechanisms that underpin ocular surface changes that increase the susceptibility to corneal erosion and infection.

Glycerol Monolaurate Inhibits Lipase Production by Clinical Ocular Isolates Without Affecting Bacterial Cell Viability.

PURPOSE: We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS: Staphylococcus aureus,Staphylococcus epidermidis,Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 10(6)/mL in varying concentrations of GML up to 25 µg/mL for 24 hours at 37 °C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS: Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dose-dependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P < 0.05) lipase inhibition above concentrations of 15 µg/mL in S. aureus and was not cytotoxic up to 25 µg/mL. For S. epidermidis, GML showed significant (P < 0.05) lipase inhibition above 7.5 µg/mL. CONCLUSIONS: Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability.

Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress.

Elevated tear osmolarity is one of the key pathological factors in dry eye leading to ocular discomfort associated with damage to the ocular surface and inflammation. The aim of this study was to determine the capacity of the organic osmolyte, betaine, to act as an osmoprotectant against hypertonic stress-induced human corneal epithelial cell shrinkage and apoptosis using in vitro cell culture models. Human corneal limbal epithelial (HCLE) cells exposed to culture medium for 16 h at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) in the presence or absence of betaine (5 or 10 mM) were evaluated for cell volume changes; cell viability; and apoptosis. Betaine (10 mM) ameliorated hyperosmotically induced reduction of cell volume (from 27% reduction to 11%) and resulted in increased mitochondrial activity (by 17%) and an increase in viable cell numbers (by 12%) compared to controls (exposure to hyperosmotic medium without betaine). Hyperosmotically shocked HCLE cells in the presence of betaine (10 mM) halved the number of damaged cells (apoptotic/necrotic) compared to cells in the absence of betaine. The presence of betaine (at 5 or 10 mM) significantly reduced the activity of caspase-8, -9 and -3/7 and release of TNF-α was also reduced by 34% or 55% after exposure of HCLE to 500 mOsm in the presence of 5 or 10 mM betaine, respectively. Using polyclonal antibody against Betaine/GABA transporter 1 (BGT-1), we detected the presence of BGT-1 in HCLE. We demonstrated that the transport of betaine was facilitated by increased osmolarity. In conclusion, betaine stabilized corneal epithelial cell volume under hyperosmotic stress and limited hyperosmotic stress-induced HCLE apoptosis.

The role of optometrists in India: an integral part of an eye health team.

India has a proud tradition of blindness prevention, being the first country in the world to implement a blindness control programme which focused on a model to address blinding eye disease. However, with 133 million people blind or vision impaired due to the lack of an eye examination and provision of an appropriate pair of spectacles, it is imperative to establish a cadre of eye care professionals to work in conjunction with ophthalmologists to deliver comprehensive eye care. The integration of highly educated four year trained optometrists into primary health services is a practical means of correcting refractive error and detecting ocular disease, enabling co-managed care between ophthalmologists and optometrists. At present, the training of optometrists varies from two year trained ophthalmic assistants/optometrists or refractionists to four year degree trained optometrists. The profession of optometry in India is not regulated, integrated into the health care system or recognised by the majority of people in India as provider of comprehensive eye care services. In the last two years, the profession of optometry in India is beginning to take the necessary steps to gain recognition and regulation to become an independent primary health care profession. The formation of the Indian Optometry Federation as the single peak body of optometry in India and the soon to be established Optometry Council of India are key organisations working towards the development and regulation of optometry.

Characterization of protease IV expression in Pseudomonas aeruginosa clinical isolates.

Expression of protease IV by Pseudomonas aeruginosa during ocular infections contributes significantly to tissue damage. However, several P. aeruginosa strains isolated from ocular infections or inflammatory events produce very low levels of protease IV. The aim of the present study was to characterize, genetically and phenotypically, the presence and expression of the protease IV gene in a group of clinical isolates that cause adverse ocular events of varying degrees, and to elucidate the possible control mechanisms of expression associated with this virulence factor. Protease IV gene sequences from seven clinical isolates of P. aeruginosa were determined and compared to P. aeruginosa strains PAO1 and PA103-29. Production and enzyme activity of protease IV were measured in test strains and compared to that of quorum-sensing gene (lasRI) mutants and the expression of other virulence factors. Protease IV gene sequence similarities between the isolates were 97.5-99.5 %. The strains were classified into two distinct phylogenetic groups that correlated with the presence of exo-enzymes from type three secretion systems (TTSS). Protease IV concentrations produced by PAOΔlasRI mutants and the two clinical isolates with a lasRI gene deficiency were restored to levels comparable to strain PAO1 following complementation of the quorum-sensing gene deficiencies. The protease IV gene is highly conserved in P. aeruginosa clinical isolates that cause a range of adverse ocular events. Observed variations within the gene sequence appear to correlate with presence of specific TTSS genes. Protease IV expression was shown to be regulated by the Las quorum-sensing system.

Transport of L-carnitine in human corneal and conjunctival epithelial cells.

PURPOSE: Previously we demonstrated expression and localization of carnitine/organic cation transporters, OCTN1 and OCTN2, in human corneal and conjunctival epithelia. The present study aimed to examine the characteristics of L-carnitine transporters in cultured human limbal corneal (HCLE) and conjunctival epithelial (HCjE) cells. METHODS: Time-course, Na(+)-dependence, kinetics, energy- and pH- dependence of L-carnitine transport were investigated by monitoring L-[(3)H]carnitine uptake into HCLE and HCjE cells. To determine the specificity of action, competition and inhibition studies were performed. RESULTS: The uptake of L-carnitine into HCLE and HCjE cells was saturable and time-dependent. An Eadie-Hofstee plot showed two distinct components: a high- and a low- affinity carnitine transport system in HCLE and/or HCjE cells. L-carnitine transport was significantly inhibited by the metabolic inhibitors (sodium azide, dinitrophenol, iodoacetic acid). The L-carnitine analogs (D-carnitine, acetyl-L-carnitine and γ-butyrobetaine), tetraethylammonium (TEA), 2-amino-2-norbornane carboxylic acid (BCH), strongly inhibited uptake of L-[(3)H]carnitine. Uptake of L-[(3)H]carnitine also required the presence of Na(+) in the external medium and the uptake activity was maximal at pH 5.5. The anti-OCTN2 antibody blocked L-carnitine uptake in both HCLE and HCjE cells whereas the anti-OCTN1 antibody did not significantly block L-carnitine uptake. CONCLUSIONS: L-carnitine is transported into HCLE and HCjE cells by an active carrier mediated transport system that is time-, Na(+)-, energy- and pH- dependent. The carnitine/organic cation transporter OCTN2 appears to play a dominant role in this process.

Contact lens deposits, adverse responses, and clinical ocular surface parameters.

PURPOSE: To correlate clinical responses during contact lens wear with the amount of protein or cholesterol extracted from lenses after wear. METHODS: Clinical parameters, including adverse response rates and corneal staining, and symptomatology rating during lens wear were collected from a series of clinical tests comprising four different silicone hydrogel lenses with four different multipurpose solutions. To test for correlates, the amount of total protein or cholesterol extracted from lenses after daily wear were compared statistically to clinical parameters. RESULTS: The amount of protein (p = 0.008) or cholesterol (p = 0.01) extracted from lenses was higher for those subjects who showed solution-induced corneal staining. Amount of protein extracted was correlated (p < 0.01) with conjunctival staining (R = -0.23), lens front surface wetting (r = 0.14), and lens fit tightness (R = -0.20). These clinical parameters accounted for 48% of lens protein deposition. The amount of cholesterol extracted from lenses was much more weakly associated with clinical variables. Amount of protein or cholesterol extracted from lenses was not associated with the production of any corneal infiltrative or mechanical adverse event during wear and was only very weakly correlated with insertion comfort of lenses. CONCLUSIONS: These results suggest that there may be no physiologically relevant consequence of cholesterol depositing on silicone hydrogel lenses. The amount of protein that deposits onto silicone hydrogel lenses during wear may have more affect on lens performance on-eye. However, the correlations were generally small and may still not indicate any causative relevant physiological response. Further work is required to determine whether there is any direct causative effect to support these correlative findings.

Role of carnitine in disease.

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.