Artificial tears for treatment of dry eye

Practitioner summary box

Artificial tears are the most frequently prescribed therapy for dry eye by optometrists and ophthalmologists[1].  They are easily accessible by patients, easy to use, and provide quick relief.  The question is though, are lubricants a treatment for dry eye, or are they merely a form of palliative care?  This article will answer these questions.

Are lubricating drops a treatment for dry eye?

A 2016 Cochrane review concluded that over-the-counter artificial tears maybe a safe and effective way to treat dry eye[2]. A new prospective, multicentre, double-masked, parallel group, randomised controlled trial by Craig et al. has shown that prolonged use of artificial tears results in significant improvements in symptoms, and signs including, non-invasive tear break up time, lid wiper epithliopathy, sodium fluorescein and lissamine green staining, and lipid layer thickness.

The study impressively found that after 6 months of treatment, 19% of patients no longer fulfilled the diagnostic criteria for dry eye disease. The authors stated that ‘This relatively late onset, but sustained change’ suggests that ‘there may be more than a simple transient effect at play’. In other words, it appears that there is a permanent therapeutic effect on the ocular surface from prolonged, consistent use of artificial tear drops. The authors hypothesised that the stabilisation of the tear film resulted in the restoration of homeostasis and a disruption of the vicious cycle of inflammation.

Clinical Summary: Lubricating drops offer treatment and not just symptom relief for dry eye.

Which dry eye drops should you prescribe?

Up until recently, it wasn’t very clear which artificial tears work best for different types of dry eye. Pucker et al. acknowledged this saying that ‘most of the literature indicates uncertainty as to which OTC artificial tear works best’[3]. Craig et al. specifically looked at lipid-based vs non-lipid-based artificial tears[4]. They found that both drops were effective at treating dry eye signs and symptoms, but that lipid-layer thickness only improved with the lipid-based drops.

Clinical Summary: For lipid-deficient tear films, lipid-based drops are recommended. Non-lipid-based drops will still have a positive effect on dry eye signs and symptoms but will not improve lipid layer thickness.

How often and for how long should you prescribe drops for?

Craig et al.’s study is a good reference when it comes to answering this question[4]. Participants in this study instilled either lipid-based nanoemulsion drops or non-lipid-based aqueous drops at least four times daily, for six months.

Sustained improvements in symptom scores were observed from day 30 onwards with an average reduction of 11 points on the OSDI scale for both drops. The results plateaued at day 30 which means that you can tell patients that although the improvements will be sustained at this point, they will not improve any further. Lid wiper epitheliopathy also improved after 30 days.

Lipid layer thickness improvement were limited to the lipid-based drops and occurred from day 90 onwards. The improvements were greater for participants who had suboptimal lipid layer thicknesses at baseline. Improvements in tear film stability and ocular surface integrity were slower and became observable after three to four drops of sustained drop use.

Clinical Summary: Patients need to be on drops at least 4 times a day for 3 to 6 months.  Symptoms will only improve after one month and signs will begin to improve after 3 months.

Do you have to prescribe preservative-free drops for dry eye patients?

The effects of preservatives on the ocular surface are will documented in the literature[5]. Hence in an eye that already has a compromised ocular surface, it is important to minimise any damage associated with preservatives. Preservative-free drops aren’t necessarily more effective than preserved drops at reducing symptoms, but they do not produce the adverse events associated with long term use of preservatives[5]. To this end, a systematic review found that there is no evidence to show that preservative-free drops are more effective than preserved drops at reducing dry eye symptoms[6].

What preservative-free drops offer patients is the ability to extend use of drops without the risk side-effects associated with preservatives[3], which would be caused by extended use of preserved drops[7, 8]. This is reflected in the preference of optometrists and ophthalmologist have in prescribing non-preserved artificial tears more than preserved alternatives[1].

Clinical summary: Chronic use of preservatives can cause damage to the ocular surface. Preservative-free artificial drops should be recommended for dry eye patients.

Artificial tears and contact lens wear

A systematic review by Pucker found that artificial tears are ‘effective for the treatment of ocular surface disease in CL wearers under most situations’[3] In terms of safety, Pucker concluded that artificial tears can be safely used with contact lenses but that more viscous and lipid-based drops have the potential to cause transient blur.

Can preserved eye drops be used with contact lenses? Pucker states that the preserved eye drops are contraindicated in contact lens wear may be outdated since current formulations use modern, high molecular weight preservatives that are relatively safe for use with contact lenses. However, he does add the caveat that, if drops needs to be used chronically, then non-preserved formulations should be chosen to avoid side-effects that are associated with excessive exposure to preservatives

Clinical summary: :  Artificial tears are safe and effective for the treatment dry eye associated with contact lens wear.  Preserved drops can be used with contact lenses but non-preserved drops should be used with dry eye patients.

Artificial tears as a protector against adverse environmental conditions

Gokul et al. found that it is possible to give some protection to dry eyes from adverse environmental conditions using artificial tears[9]. Single application of both lipid and non-lipid containing eye drops conferred protective effects against exposure to adverse environmental conditions in subjects with mild-to-moderate dry eye, although the lipomimetic demonstrated superior prophylactic efficacy.

Both therapies resulted in increased NIBUT (both p < 0.001), and prevented its decline below baseline with simulated adverse environment exposure (both p > 0.05). However, only the lipomimetic drop increased LLG (p < 0.001) and precluded its fall below baseline post-adverse environment exposure (p =0.15). Furthermore, post-instillation and post-exposure LLGs and NIBUT were significantly higher in the lipomimetic group (all p < 0.05). No significant changes were observed in glare acuity, TVF and TMH (all p > 0.05). More subjects (67%) reported greater ocular comfort in the eye receiving the lipomimetic.

Clinical Summary: Lubricating drops, particularly lipid-based drops, can help prevent signs and symptoms of dry eye related to exposure to adverse environmental conditions.

References

1. Xue, A.L., et al., A comparison of the self-reported dry eye practices of New Zealand optometrists and ophthalmologists. Ophthalmic Physiol Opt, 2017. 37(2): p. 191-201.
2. Pucker, A.D., S.M. Ng, and J.J. Nichols, Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database of Systematic Reviews, 2016(2).
3. Pucker, A.D., A review of the compatibility of topical artificial tears and rewetting drops with contact lenses. Contact Lens and Anterior Eye, 2020.
4. Craig, J.P., et al., Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial. Ocul Surf, 2021: p. 62-69.
5. Walsh, K. and L. Jones, The use of preservatives in dry eye drops. Clinical ophthalmology (Auckland, NZ), 2019. 13: p. 1409.
6. Ribeiro, M.V.M.R., et al., Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review. Arquivos brasileiros de oftalmologia, 2019. 82(5): p. 436-445.
7. Bernal, D.L. and J.L. Ubels, Quantitative evaluation of the corneal epithelial barrier: effect of artificial tears and preservatives. Current eye research, 1991. 10(7): p. 645-656.
8. Schaefer, K., et al., A scanning electron micrographic comparison of the effects of two preservative-free artificial tear solutions on the corneal epithelium as compared to a phosphate buffered saline and a 0.02% benzalkonium chloride control, in Lacrimal Gland, Tear Film, and Dry Eye Syndromes. 1994, Springer. p. 459-464.
9. Gokul, A., M.T. Wang, and J.P. Craig, Tear lipid supplement prophylaxis against dry eye in adverse environments. Contact Lens and Anterior Eye, 2018. 41(1): p. 97-100.