Paul McCann, Bill Vaughan, Genie Han, Rebecca Petris, Darren Gregory, Tianjing Li
Which eye problem can develop due to an underlying health problem, or due to a previous eye treatment, or even due to no apparent reason at all? Which eye problem affects almost twice as many women as men? Finally, which eye problem may have been worsened during the COVID pandemic?
The answer to these questions — Dry eye disease. No trivial problem, as you will know if you have ever had it, dry eye is present in about 7% of American adults (that is about 16.4 million Americans).1
What is dry eye?
The surface of our eyes is moist and is covered in a thin layer of tears. When there are problems with this layer of tears, people can develop the condition called dry eye disease. People with dry eye may feel discomfort, as though they have something in their eye, they may have burning sensations, or they may be sensitive to light. They can also have blurred vision and fluctuating vision which can affect driving and reading. Dry eye can really hurt your quality of life and even hurt your income because of reduced productivity. Here, we describe the condition and review the best available science to try to answer if there is a good way to treat it.
The mechanisms of dry eye disease are important to understand the treatment choices that are available. Mechanisms of dry eye disease include inadequate tear production, excessive tear evaporation, and a mixture of the mechanisms. Inadequate tear production occurs when there is reduced secretion of the water (aqueous) component of tears. This can be due several reasons including, prescription drug side effects or autoimmune conditions such as rheumatoid arthritis in which the body’s defence mechanisms become overactive and mistakenly attack the tear producing glands.
Excessive tear evaporation is mostly due to abnormalities in the oily (lipid) content of the tears. Small glands called Meibomian glands sited within the eyelids produce this lipid component and open onto the surface of the eye at the eyelash base where the secreted lipid mixes with the aqueous component of the tears to prevent excessive tear evaporation. Meibomian gland dysfunction (MGD) leads to disruption of the quality and volume of the secreted lipid and is a major cause of dry eye disease. The exact cause of MGD is not fully understood but it occurs when the lipid forms a turgid toothpaste consistency instead of a healthy olive oil consistency. This change in the quality of the lipid reduces the quantity secreted and can progress to irreversible destruction of the gland itself.
Who are we?
We are researchers working for the Cochrane Eye and Vision group (CEV) based across the University of Colorado Anschutz Medical Campus and Johns Hopkins University. As part of the Cochrane network, at CEV, we collect and review the best scientific research on eyes in a systematic way according to the trusted practices of Cochrane.
What is Cochrane?
It is a worldwide collaborative network of health researchers, named after a late Scottish doctor and epidemiologist, Archie Cochrane, who promoted the use of randomized clinical trials as the ‘gold standard’ of evidence on what works and doesn’t work in your health.
What is the Cochrane evidence for dry eye disease?
We have conducted six Cochrane systematic reviews which look at the effectiveness and safety of dry eye treatments. Obviously, we need more good research – as we will talk about later.
Three reviews address the effectiveness of three different types of eye drops, (1) over the counter (OTC) artificial tears, (2) cyclosporine A eye drops and, (3) autologous serum eye drops. The remaining Cochrane systematic reviews address the effectiveness of three other treatments including, punctal plugs, omega-3 and omega-6 polyunsaturated fatty acids, and intense pulsed light (IPL) therapy for MGD.
OTC artificial tears2
OTC artificial tears aim to replenish the tears at the surface of the eye. Although they attempt to mimic the role of natural tears, OTC artificial tears lack the biologically active components found naturally. They are typically the first-line treatment for dry eye and the Cochrane systematic review suggests that they may provide symptomatic relief. However, no strong conclusion can currently be made about which formulation is best. OTC artificial tears are generally safe but may very occasionally cause side-effects including irritation, reddening, and taste alterations. Side-effects to OTC artificial tears are known to be associated with chemical preservatives such as benzalkonium chloride. Preservatives are used in some multi-dose eye drop containers to prevent contamination. Preservative-free artificial tears are now available, both in single dose applicators and multi-dose containers but, although these are much better tolerated, they are more costly.
Cyclosporine A eye drops3
Cyclosporine A eye drops aim to dampen inflammation at the surface of the eye, a major factor in the dry eye disease process. The Cochrane systematic review suggests that cyclosporine A eye drops combined with OTC artificial tears may provide better symptomatic relief of dry eye compared with OTC artificial tears alone, however, the evidence is uncertain. In addition, cyclosporine A eye drops are much more likely to be associated with bothersome side effects such as burning and stinging sensations.
Autologous serum eye drops4
Autologous (meaning using your own cells or tissues to treat your own problem) serum eye drops are made by separating the liquid component of a patient’s own blood from the cells in the blood. They aim to provide lubrication at the eye surface as well as provide nutrients that allow them to mimic natural tears more closely. Application of autologous serum eye drops has gained popularity as a second-line therapy for dry eye over the past decade. The Cochrane systematic review suggests that autologous serum eye drops may be effective in relieving the symptoms of dry eye compared to OTC artificial tears in the short term (2 weeks). However, there was no evidence of benefit after longer term treatment because study follow-ups were not performed beyond 4 weeks. Production, preparation and storage processes for autologous serum eye drops are more complex than for other commercially available eye drops. No forms of autologous serum are commercially available. Therefore, patients must be well enough to tolerate blood donation and may need to undergo prior testing for blood borne viral diseases. The use of autologous serum eye drop therapy by clinicians may also be subject to special regulations.
Punctal plugs5
Punctal plugs are tiny collagen or silicone plugs which are placed in the tear drainage ducts at the doctor’s office. They aim to maintain the pool of natural tears on the surface of the eye longer by preventing tears draining away thereby preserving moisture and lubrication. The Cochrane systematic review suggests that punctal plugs do not conclusively improve dry eye symptoms and it is still unclear if they are better than eye drops such as cyclosporine A or OTC artificial tears. Also, punctal plug effectiveness possibly varies depending on the underlying cause of dry eye, the severity of the disease and the characteristics of the plug, i.e., size, shape and material used. Furthermore, punctal plugs may be associated with side effects such as watery eyes or infection and swelling of the tear sac adjacent to the nose.
Omega-3 and omega-6 polyunsaturated fatty acids6
Omega-3 and omega-6 polyunsaturated fatty acids are essential oils which can be consumed as part of a well-balanced diet or as nutritional supplements. They are generally considered to be low risk interventions in healthy adults when taken in moderation. Taking in more of these oils seems to fight inflammation and therefore a correct balance of polyunsaturated fatty acid intake may have an anti-inflammatory effect in dry eyes. Furthermore, omega-3 and omega-6 intake may also be protective of the glands which secrete the lubricating lipid layer of the tears. The Cochrane systematic review suggests a beneficial effect on dry eye symptoms when omega-3 supplements were combined with standard dry treatments (e.g., OTC artificial tears) compared to standard eye drop treatments alone, and when omega-3 supplements were compared to omega-6 supplements. Overall, omega-3 supplements may have a role in managing dry eye but the current evidence is uncertain and inconsistent. Sorry it is not a definite answer!
Intense pulsed light (IPL) therapy7
For the treatment of MGD, IPL is applied to multiple (typically five or six) locations across the face and under the lower eyelids. Typically, a course of treatment is recommended, involving three or four IPL sessions over approximately four months. IPL uses a high-output flash lamp, to produce a broad wavelength, non-coherent light for brief flashes through a gel applied to the skin. It is thought that IPL works by liquefying turgid Meibomian gland secretions, reducing local inflammation and improving the structure of the Meibomian glands. The Cochrane systematic review reported conflicting evidence regarding reduction in dry eye symptoms. Results of two combined studies found no improvement in dry eye symptoms but results of one other study, not combined, reported a reduction in symptoms in favour of IPL. The Cochrane review also suggests IPL may be helpful to improve some of the clinical signs of MGD such as tear stability and tear composition. Overall, the evidence for how effective IPL is for treating MGD was of low or very low quality. The results of the 14 studies currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD.
Your doctor may also prescribe eye drops that contain steroids for treating your dry eye; a Cochrane systematic review on this topic is underway.
Summary and conclusions
Cochrane systematic reviews of the scientific information about health problems are trusted sources of literature for healthcare professionals and their patients, and we are in the process of trying to make our scientific consensus studies on many different eye problems available in plain, easy-to-understand language. If you want to see the full reports on which this summary is based, check us out at /.
In summary, dry eye is a relatively common eye condition which can significantly impact upon a person’s quality of life and productivity. Currently there is no cure for the condition and the evidence for the effectiveness of available treatments shows a mixed picture. This makes treatment decisions difficult for patients and physicians alike. Patients may need to take a trial-and-error approach in collaboration with their healthcare provider to find a treatment option that suits their needs. We know it is frustrating that there are often no clear and easy answers and solutions.
Despite the lack of clarity on which treatment is most effective, the current body of evidence yields important information and directs us towards opportunities for the future. Evaluation of the quality of the primary studies included in the systematic reviews has highlighted shortcomings in study designs and these can be minimised or avoided in future studies. Patients can make crucial contributions to the ongoing effort to find effective treatments for dry eye by advocating for better quality primary studies and participating in well-designed future research studies.
References
1. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017;182:90-98. doi:10.1016/j.ajo.2017.06.033
2. Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016;(2). doi:10.1002/14651858.CD009729.pub2
3. de Paiva CS, Pflugfelder SC, Ng SM, Akpek EK. Topical cyclosporine A therapy for dry eye syndrome. Cochrane Database Syst Rev. 2019;(9). doi:10.1002/14651858.CD010051.pub2
4. Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017;(2). doi:10.1002/14651858.CD009327.pub3
5. Ervin AM LA, Pucker AD. Punctal occlusion for dry eye syndrome. Cochrane Database Syst Rev. 2017;(6). doi:10.1002/14651858.CD006775.pub3
6. Downie L, Ng SM, Lindsley K, Akpek EK. Omega‐3 and omega‐6 polyunsaturated fatty acids for dry eye disease. Cochrane Database Syst Rev. 2019;(12). doi:10.1002/14651858.CD011016.pub2
7. Cote S, Zhang A., Ahmadzai L, et al. Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction. Cochrane Database Syst Rev. 2020;(3). doi:10.1002/14651858.CD013559