Dry Eye & Lifestyle A Report from the Tear Film & Ocular Society

The report comprised the findings of eight topic area subcommittees, along with those of three supporting subcommittees – the Evidence Quality, Industry Liaison and Public Awareness committees.

studies are needed to examine the effects of cosmetic ingredients and to develop guidelines to assess their safety and tolerability on and near the eye surface

The reports are the work of 158 participants from 38 countries over two and a half years. The aim is to ensure optometrists can draw on the latest evidence when providing patients with advice about the influence of lifestyle factors on dry eye disease, and determining the best approach to management.

In this article, Dr Jennifer Rayner summarises the findings from each of the eight topic areas discussed in the workshops.

Contact Lenses

There are concerns that unregulated suppliers of contact lenses (CLs), and particularly those of coloured CLs, may be associated with poorer patient education and a lack of follow-up appointments, especially in younger wearers who are prone to be less compliant with CL care and replacement. This carries an increased risk of CL complications.

Patients with allergies can wear CLs, but further research is needed to provide evidence linking when people are unwell with any increased CL complications. This is important as the future use of CLs may be as biomarkers to aid diagnoses, or as drug delivery systems for allergy, ocular surface inflammation, and diseases, such as glaucoma are on the horizon.

Ocular surface discomfort and complications with CL wear can be affected by systemic diseases, such as diabetes and thyroid disease, and the medications used to treat them; by the patients’ age (younger patients do better); and the length of CL wear.

Environmental factors, such as low humidity, pollution, high altitude, wind and dust can contribute to CL discomfort. Decreasing air temperature and humidity leads to a thinner, less stable pre-lens tear film that is prone to more evaporation and dryness, which impacts vision and comfort. However, more studies are needed as much of the research was carried out on materials no longer used.

Our growing global dependence on digital devices (over 50% of the global population are internet users) can result in decreased blink frequency and amplitude, leading to eye strain, dry eyes, and blurry vision.

CLs should also be fully corrected for optimum performance and quality of life – i.e., fitting multifocal lenses and correcting astigmatism and keratoconus – in young, adult, and elderly patients.

The workplace can be problematic with fumes, vapours, aerosol droplets, and make-up causing irritation with CL wear. Additionally, activities such as smoking tobacco and marijuana, vaping, or being under the influence of drugs or excessive alcohol can cause inflammatory or infective complications.

Although there are no direct reports of stress, depression or physical inactivity negatively affecting CL wearers, there is an association of these conditions with dry eye sufferers. With the known link of dry eye disease (DED) and decreased CL comfort, this could be a link that is worthy of potential research.

Finally, collaborative efforts between manufacturers, eye care professionals, and consumers can facilitate environmentally friendly production and disposability of the raw materials and final products.

Cosmetics

There is no global consensus on the definition of cosmetics, as it varies across countries and regions. Cosmetics or ‘make-up’ can include creams, concealers, eyelash extensions, eyeliners, foundations, mascara, serums, glues, and removers. Their purposes include concealing, preserving, buffing, exfoliating, gluing or plumping to name a few.

There are also products such as botulinum toxin, fillers, chemical peels, platelet-rich plasma (PRP), tattooing, dyeing, perming, and micro needling that can be harmful to the adnexa and ocular surface. In particular, procedures involving the lashes such as curling, tinting or extensions can have adverse events. Eyelash extensions can be associated with allergic contact dermatitis, loss of eyelashes, calcification of the lash base, blepharitis, conjunctivitis, corneal abrasions, and keratitis. Indeed, the fibres can break off, requiring surgical removal from the subconjunctiva and there are reports of lashes catching fire during surgery as the fibres are flammable.

Sharing make-up can lead to bacterial, viral, and demodex contamination. This is related to personality traits of users, as well as the amount and age of the products used.

Parabens are preservatives included in more than 22,000 products sold in the United States, including in shampoo and skincare products. These are toxic to human corneal, conjunctival, and meibomian gland (MG) epithelial cells in vitro. They are allergens and endocrine disruptors that possess oestrogen potency and anti-androgen activity, and they may increase the risk of malignancies.

Phthalates – used as solvents in makeup removers, nail polish, fragrances, and in packaging – can leach into products unintentionally. They can adversely affect corneal endothelial cell growth and viability and they are linked to endocrine disruption and reproductive disorders, cardiovascular disease, precocious puberty, hepatoxicity, neurotoxicity, and sleep problems. Phthalates are banned in Europe but not in the US.

Benzalkonium chloride (BAK), commonly used in eye drops and in make-up, has been shown to be toxic to ocular surface cells in vitro, in amounts that are 20,000-fold lower than approved levels in eye make-up. They may induce tear film instability, goblet cell loss, conjunctival squamous metaplasia, and apoptosis, as well as disruption of the corneal epithelial layer. Application to the ocular surface can increase the prevalence of itching, blepharitis, and MG loss.

Formaldehyde can be mutagenic, carcinogenic, and pro-allergenic, and in levels 2000-fold lower than the European Union (EU) limits for cosmetics, it is toxic to corneal, conjunctival, and MG epithelial cells.

Tea tree oil (TTO) and terpinene-4-ol (T4O), commonly used to treat anterior blepharitis, is an endocrine disruptor with oestrogen and anti-androgen activity that may induce MG dysfunction. It is toxic to human MG, corneal, and conjunctival epithelial cells within 90 minutes in vitro. It may contribute to the development of antibacterial resistance to human pathogens and commensals. It also may induce prepubertal gynaecomastia in boys. In fact, the EU Cosmetic Toiletry and Perfumery Association states that it shouldn’t be used in cosmetic products in a way that results in a concentration of greater than 1% being applied to the body.

Recommendations are that further robust, well-controlled studies are needed to examine the effects of cosmetic ingredients and to develop guidelines to assess their safety and tolerability on and near the eye surface.

Packaging needs to contain information, such as product toxicity, durability, and indications, and there is a need to standardise definitions of words such as ‘natural’ and ‘clean’.

Digital Environment

Our digital environment can be defined as any technology requiring viewing of the digital display for a cognitive task and where digital eye strain (DES) is the development or exacerbation of recurrent ocular symptoms (OS) and/or signs, related specifically to digital device screen viewing.

Characteristics that can influence users’ experiences include the digital display style, light emission, screen size, position, and resolution, as well as refresh rate, viewing distance / resolution, and screen brightness / contrast. The intensity of the activity, including screen time, cognitive demands, and lack of breaks, as well as CL use, sleep time, the environment, age, sex, and blink patterns (frequency / amplitude / ocular surface exposure) can contribute to DES. Common symptoms include fatigue, tired eyes, eyestrain, and burning.

The global prevalence of DES is estimated to be 70.7%, but this is highly dependent on diagnostic criteria, with most studies using the computer vision syndrome questionnaire CVS-Q for measurement. This has limitations, as only one symptom is required and it is not exclusive to digital use. There is currently no robust algorithm to diagnose DES and many people ‘diagnosed’ with DES probably have DED, under corrected/not fully corrected refractive error and /or a binocular vision anomaly, which have their own diagnostic criteria and established evidence-based management strategies. Until further evidence is available, we can only confirm that a patient has DES if they only develop or have increased signs or symptoms when using digital devices.

We know that topical eye preparations with preservatives can cause toxic, allergy, and immune-inflammatory effects

The most likely strategy to have a positive effect on DES is oral omega-3 supplementation. Probable strategies, requiring more evidence, include correcting refractive error, screen distance, regular blink and break reminders, appropriate ergonomics, increased screen / font size, increasing humidity / decreasing air conditioning, and limiting screen time to four to five hours.

There is no evidence that blue-light blocking, antioxidants or progression addition computer glasses are effective. Oculomotor exercises, yoga, traditional medicines, and dry eye treatments had limited research.

Elective Medications

The term ‘elective’ in the medical field is defined as “planned or undertaken by choice with a lower grade of prioritisation”.

We know that topical eye preparations with preservatives can cause toxic, allergy, and immune-inflammatory effects. More natural products, such as aloe vera and Manuka honey, can cause localised redness and irritation.

Antihistamine and non-steroidal anti-inflammatory drugs (NSAIDs) can cause ocular irritation, stinging, visual disturbances, and redness. The effects from lid hygiene products, such as those containing tea tree oil, can affect MG epithelial cells. Even sunscreen can cause irritation, redness, and tearing and nanoparticles of titanium dioxide and zinc oxide can be toxic to corneal cells in animal models.

When it comes to treatment of acne and rosacea, glycolic and salicylic acids, ivermectin, and isotretinoin can cause punctate epitheliopathy, affect ocular surface disease index (OSDI) scores, and decrease MG function. Systemic medications can damage the ocular surface by affecting the lacrimal, meibomian gland, and goblet production, and can affect the innervation, vascularity, tissue metaplasia, inflammation, and neurosensory components of target organs. Other medications that can be deleterious to the ocular surface include corticosteroids, antimicrobials, vitamin supplements, hormone replacement therapy, antihistamines and anticholinergics, antidepressants, opioid agonists, and antivirals. In fact, cold medications (including NSAIDs) and allopurinol and carbamazepine have been known to induce a systemic immune response, resulting in Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN).

Elective ocular surgical procedures, such as corneal cross linking, phaco and intraocular lens implants, and pterygium excision, can all have potential ocular surface effects. Ptosis and blepharoplasty surgery in particular, could cause changes to blink patterns and lid positions. In laser refractive surgery, 59.4% of patients who underwent LASIK reported dry eye symptoms at 30 days post-operatively. The studies vary when it comes to whether there is a lower risk of dry eye with a flap created with a femtosecond laser versus a mechanical microkeratome, but the flap depth, size, and hinge location can affect the development of dry eye, and LASIK causes less damage to corneal nerves than photorefractive keratectomy.

Non-surgical procedures, such as Botox, intense pulsed light (IPL), high frequency ultrasound or radio waves, and thermal pulsation treatment can be associated with dry eye signs and symptoms, especially if the eyes are not adequately protected when undergoing IPL, for example. Even procedures including radiation, neurosurgical, and bariatric surgery can be risk factors for dry eye. The recommendation was to make our patients better aware of the risks, benefits, and consequences when deciding on elective procedures and medications.

Environmental

The subcommittee decided to review the evidence of environmental risk factors that have an impact to the ocular surface. Environmental conditions were divided into two subgroups:

Climate related: temperature, humidity, wind speed, altitude, dew point, UV light and allergens, and Outdoor and indoor pollution: gases, particulate matter, and other sources of airborne pollutants.

Extremely high or low temperatures can affect the ocular surface homeostasis associated with DED; indeed high temperature is an important factor in the transmission of trachoma from eye seeking flies. There is a negative association between low humidity and the risk of DED, and moisture goggles can improve ocular comfort and decrease tear evaporation.

There is limited evidence on the effect of wind speed on ocular surface disease, however, it is a recognised issue for people in sub-zero temperatures, such as those working in Antarctica or even during some ultramarathon runs.
Long-term conditions associated with altitude are cataracts and dry eye, and short-term effects can be corneal thickening and photokeratitis. The most common long-term condition is pterygium. Pterygia also has a higher prevalence from ultraviolet (UV) exposure at lower altitudes and supra threshold exposure can cause photokeratitis, ocular and peri-ocular malignancies, and climatic droplet keratopathy.

High dew points are correlated with tear break-up time (TBUT) and may be a protective factor.

A critical limitation to studies is that exposures to environmental pollutants are difficult to measure and standardise. Indoor and outdoor allergens, such as grasses, dust mites, and pet dander, can cause allergic conjunctivitis.

Air pollution containing gases such as nitrogen dioxide, and particulate matter such as volcanic ash (9% of the global population live within a potential zone of active volcanic eruption), is correlated with DED and conjunctivitis. Coal dust exposure is associated with decreased tear production and TBUT.

Indoor pollution can lead to a condition now recognised as sick building /sick house syndrome where air conditioning, humidity, construction materials, toluene and paint thinners, mould and particulates, among other factors, create health effects that can be directly linked to time spent in a building.

Ocular surface injuries can occur from occupational exposure such as alkali products and pesticides, from household exposure to cleaning products, superglue, Chuna in India (a limestone powder used for digestive restoration), and even pepper spray or acid exposure in criminal activity.

Ocular surface neoplastic disease has a high recurrence rate. Predisposing factors include UV and cigarette smoke exposure. Increasingly more frequent and extreme weather events, such as heat, drought and heavy rain, alter the burden and pattern of the distribution of vectors – both water and air-borne – with an indirect influence on nutrition, poor mental health, violence, and conflict.

Lifestyle

Most studies were epidemiological. A 2017 meta-analysis found there was increased prevalence of depression in individuals with DED, and DED symptom scores were significantly associated with depression severity scores. The data is weaker when looking at signs of DED, such as TBUT, and corneal staining. Although both depression and anxiety may be linked to the DED umbrella with biologic plausibility, the DREAM study showed no relationship between DED signs /symptoms and antidepressants.² Several studies showed a link between anxiety and dry eye diagnosis, but the results were less uniform when examining signs.

Several population-based studies showed a person’s poorer perceived health status and increased psychological stress was associated with an increased odds ratio of aqueous deficient and evaporative DED. They also showed an association between stress and symptoms. A meta-analysis of 19 articles looked at sleep patterns – a physiological process can impact the immune, metabolic ageing, psychiatric, and cardiovascular metrics – and it showed that those with DED have poorer sleep quality, sleep less, and experience more sleep disturbances than controls. Sleep deprivation can lead to epithelial disruption, lipid accumulation, microvilli morphological changes, and decreased tear production. Resting for 14 days after the sleep interruption reversed the observed changes.

Studies also show an increase in DED prevalence among continuous positive airway pressure (CPAP) users versus the general population, with ‘floppy eyelid syndrome’ being the most common clinical sign. Obesity was linked to abnormalities in MG function and architecture, but co-morbid conditions, such as sleep apnoea may contribute to the noted association.

COVID-19 made mask wearing a norm in the general population more recently and mask wear exacerbated DED symptoms when worn six or more hours a day, five days per week.

Eye rubbing and keratoconus research was found to be conflicting, but polycystic ovarian syndrome and complete androgen insufficiency showed an increase in DED signs and symptoms. There is some evidence that hormonal changes in pregnancy can transiently increase DED. Evidence supports a co-morbidity between chronic pain conditions – such as migraine, fibromyalgia, irritable bowel disease, and back pain – and DED (mostly for symptoms), although the quality of evidence is low. The link between DED and tobacco smoke was contradictory and although limited, data for long-term cannabis use indicated a decrease of corneal endothelial density. Alcohol consumption may contribute to DED but may also be part of a wider issue, which involves poor nutrition (i.e., Vitamin A deficiency). Two studies indicated an increase of Schirmer production and tear meniscus after caffeine intake.

Nutrition

A poor diet is the second highest risk factor of death and disability, with over-nourishment exceeding that of under-nourishment. The committee looked at the effect of nutrition and the ocular surface. Omega-6 can be proinflammatory, and there is a 2.5x increased risk of DED with increased Omega-6, whereas there is a 30% decrease in risk with every gram of Omega-3 (anti-inflammatory) consumed.

There is strong evidence that vitamins A, B12, C and D play a positive role in DED, and limited evidence of the beneficial effects of olive and primrose oils, as well as selenium and lactoferrin. Although there is a strong correlation between plasma and tear osmolarity, there is no change in tear flow and water intake is not protective for dry eye. Chemicals, such as parabens and bisphenol A (BPA), can be endocrine disruptors and can change the diversity of the gut biome. Mercury compounds can increase tear osmolarity, cytokine production, and cause nerve changes; and a single episode of alcohol consumption can increase tear osmolarity and pain and decrease TBUT.

Food intolerances and allergies can increase the risk of dry eye, as well as non-allergic rhinitis and allergic conjunctivitis. With regards to diets, the Mediterranean diet, with its anti-inflammatory effects, showed improvement in both signs and symptoms of dry eye at six months from baseline. There is a lack of high-quality evidence when it comes to the effects on the ocular surface of intentional food restriction, such as anorexia nervosa and fasting.

When it comes to dietary supplements, caffeine has been shown to offer a protective effect, vitamin A and curcumin have been shown to decrease dry eye symptoms, and birch pollen honey has been shown to decrease allergy symptoms. The gut biome plays an important role in regulating low-grade chronic inflammation and both gut dysbiosis and reduced gut microbiome diversity is more prevalent in dry eye. Both pre- and pro-biotics can improve the signs and symptoms of dry eye. Finally, conditions such as obesity, bariatric surgery, metabolic syndrome, pre-diabetes, and type 2 diabetes can all affect the ocular surface, whereas dyslipidaemia has conflicting evidence, and hypertension is associated with a low risk of DED. There is significant evidence that good nutrition impacts the ocular surface, however that evidence is in its infancy.

Other challenges, such as types of employment, incarceration, water and sanitation, housing conditions, education, poverty and socioeconomic status can also have an impact on the ocular surface

Societal

This report looked at the digital world, regional / socioeconomic / and cultural environment, our living and working conditions, our individual lifestyle and social factors, and our biology and genetic factors.

It anaylsed the impact of nutrition such as food insecurity, vaping and smoking, exercise, chemicals such as alcohol, caffeine and recreational drugs, recreational and sports activities, and the influence of societal pressures that result in elective surgery such as Botox and lid procedures.

Other challenges, such as types of employment, incarceration, water and sanitation, housing conditions, education, poverty and socioeconomic status can also have an impact on the ocular surface.

As well, factors such as remoteness to services, the availability and affordability of services including those that are culturally and sex /gender appropriate, the effects of air quality and the impact of food and water security with climate change, and the effects of war and conflict, violence, and displacement (which can include access to food /water as well as exposure to chemicals such as tear gas) means that ocular surface disease is deprioritised.

As for the digital world, the workshop looked at how compliance to treatment regimens could be impacted by mental, physical, and social health, as well as practitioner specific issues – which impact the accessibility or quality of health delivery – together with health apps. Finally, the effects of the pandemic have resulted in delays in diagnosing and treating ocular surface disease, the onset of mask-associated dry eye (MADE), increased screen time due to remote learning, and injuries from hand hygiene measures, all of which have negatively impacted ocular surface disease. However, access to online health platforms and apps, as well as telehealth, have enhanced compliance to treatment.

To read the TFOS Lifestyle – Evidence quality report: Advancing the evaluation and synthesis of research evidence in greater detail, visit: pubmed.ncbi.nlm.nih.gov/37054912.

Dr Jennifer Rayner BAppSc (Optom) GradCertOcTher (UNSW) was a registered nurse before studying optometry. She has practised as an optometrist since 2003 and with her business partner Dr Rene Malingre, established South Australia’s first dedicated dry eye clinic, Alleve Eye Clinic, in 2016. Dr Rayner is a committee member of the Tear Film and Ocular Society.

References
1. Downie, L. E., Britten-Jones, A. C., Hogg, R. E., Jalbert, I., Li, T., Lingham, G., Liu, S-H., Qureshi, R., Saldanha, I. J., Singh, S., and Craig, J. P. (2023). TFOS Lifestyle – Evidence quality report: Advancing the evaluation and synthesis of research evidence. The Ocular Surface, 28, 200-212.doi.org/10.1016/j.jtos.2023.04.009
2. Hussain M., Shtein R.M., Pistilli M., Maguire M.G., Oydanich M., Asbell P.A., DREAM Study Research Group. The dry eye assessment and management (DREAM) extension study – A randomized clinical trial of withdrawal of supplementation with omega-3 fatty acid in patients with dry eye disease. Ocul Surf. 2020 Jan;18(1):47-55. doi:10.1016/j.jtos.2019.08.002. Epub 2019 Aug 16. PMID:31425752; PMCID: PMC7004875.