Ask any clinician whether patients routinely present with dry eye symptoms on a daily basis and you are likely to be greeted with an emphatic yes. The number of people around the world with a diagnosis of dry eye is growing at almost 3 per cent per year and it is estimated that there will be 250 million people suffering with symptoms by 2022.1
In the UK the prevalence is estimated to be approximately one in five adults,2 but this is the people with a confirmed diagnosis and probably represents just the tip of the iceberg; there are likely to be many more affected by what we would call ‘episodic’ dry eye. This would present itself, when working on computers or tablets, when wearing contact lenses, with exposure to air conditioning, and related to many other external influences. A recent study demonstrated that one in 10 British women have a diagnosis of dry eye disease, but one in five experience symptoms.3 The prevalence of dry eye problems increases through life with every decade, and dryness remains one of the most common eye complaints among the elderly.4,5
Ideal formula
With this ever-increasing demand for symptomatic relief, it is easy to see why there appears to be an abundance of topical over-the-counter preparations available in optometric practices, pharmacies and, increasingly, supermarkets. Patients confronted with so many options (often without any clinician recommendation) adopt a ‘they are all the same’ attitude, and make a choice of product based on packaging and branding, not necessarily performance or constituents. However, a new generation of formulations is now emerging that, in my view, prove that not all dry eye drops are the same.
In the course of my daily clinic I discuss dry eye management with most patients, and discuss causative influences ranging from lifestyle and environmental effects, to systemic and medication effects. I am always interested in new advances in symptomatic treatments in this field and look out for products with a good scientific basis underlying their formulation.
In particular I am interested in a formulation offering the following features:
- A preservative-free preparation. This is in line with the key advice compiled from the Dry Eye WorkShop Report (DEWS)2
- A preparation that mimics the same viscoelastic properties of the tear film (changing in viscosity between blinks)
- A preparation that addresses the issue of tear hyperosmolarity associated with dry eye, and thereby protects the ocular surface for as long as possible
- A bottle that can be used easily and will aid compliance.
Effective combination
With these criteria in mind, I was excited to try out Thea’s latest offering, Thealoz Duo (Figure 1) – a combination of two of its most popular dry eye drops – hyaluronic acid (0.15 per cent) and trehalose (3 per cent) in a hypotonic formulation. Hyaluronic acid (HA) features in several modern dry eye drops because of its superb water-holding properties and viscoelastic behaviour, making it an ideal choice over purely ‘cellulose-based’ products.
HA is known to have the following beneficial properties:
- Prolonged residence time across the ocular surface in comparison to other dry eye drops6,7
- Ability to improve the stability of the tear film due to its viscoelastic properties8
- Studies have shown that hypotonic formulations of HA eye drops are better at relieving symptoms compared to isotonic formulations9,10
- Research suggests that sodium hyaluronate has a beneficial effect on the conjunctival epithelium11,12
Another beneficial property of HA is that is naturally found in the human body – in our joints, skin and even the eye itself.
Trehalose is a natural disaccharide found in bacteria, insects, plants and invertebrates and offers the following benefits:
- Protects corneal epithelial cells from death due to desiccation 13,14
- Confers resistance upon tissue to high osmolarity environments, protecting proteins and membranes from denaturation 15,16
- Protects corneal cells prior to Lasek 17
Research has revealed that trehalose plays a major role in cell survival in dehydrating environments and protection against oxidative and other stresses in many organisms, including when applied to mammals. It is believed to do this by stabilising the proteins and lipids in cell membranes particularly, and therefore protecting cells. In fact, trehalose is widely employed as a protector in freeze-dried oocytes for in vitro fertilisation.18 Because it is a disaccharide, trehalose is antigenically inert and can be safely used as a topical agent.18
Its use as an excipient in injectable protein drug formulations (such as the anti-VEGF drugs Avastin and Lucentis) confirms its safety when administered to the human eye. Currently, trehalose (tradename Thealoz) is most commonly used in the management of chronic dry eye sensations and fatigue caused by external factors such as wind, smoke, pollution, dust, dry heat, air conditioning, aeroplane environments, or by long hours working in front of a computer screen. Its protective properties extend to direct ‘osmoprotection’ for cells.
Breaking the cycle
The concept of a vicious circle in dry eye disease is one that is now generally accepted and really helps us to understand the common triggers and how we might manage someone out of this cycle. Effective products should be able to interrupt this cycle at one or several points. Thealoz Duo offers a hypotonic, preservative-free formulation that is viscoelastic, with HA to hydrate and lubricate, and trehalose to protect. The combined effect appears to be better than the sum of its parts, with several patients reporting that it lasts longer than any drop tried previously. Of particular interest is that this response has been reported in both aqueous deficient and evaporative dry eye patient groups.
In my view, Thealoz Duo appears to tick all of the boxes clinically, being suitable for both categories of dry eye, making a guided clinical recommendation that much easier.
What the people say
Optician is based at a large office block in Sutton and the many staff working here are almost all seated for at least part of the day at a computer screen. The office is air-conditioned and, in keeping with periodical publications, staff are often required to work prolonged hours in order to meet deadlines. Workers here represent a useful pool of potential dry eye sufferers and it was no surprise that there was a keen response to a request for volunteers to offer feedback on the new Thealoz Duo drops.
Thirty staff of varying ages (from 23 to 70 years, 25 female) and with dry eye symptoms agreed to submit answers to a short questionnaire and then to try the drops for two weeks. All had symptoms that increased in severity over the working day; 21 had symptoms outside the office, and all had at some stage tried one or more ocular lubricants of various formulations in the past with some degree of success. When asked to rate the symptoms when at their worst, as a score of 1 (mild irritation) to 5 (severely gritty, burning), the staff confessed an average score of just over 3.
Perhaps not surprisingly, all reported a positive impact when using the Thealoz Duo. All used the drops to alleviate symptoms rather than as a prophylactic measure. Each were asked to state any comments about their experience with the drops. Here are a just a snapshot of responses:
- ‘I found the drops easy to put in and my eyes felt better straight away’
- ‘Immediately soothing’
- ‘It may sound strange but other drops sometimes taste funny after I use them. These didn’t’
- ‘I didn’t have to use the drops as often as others I have bought’
Not a scientific study, but a useful snapshot of a positive response from a demanding audience.Optician and participants had no inducement or financial gain from this simple trial other than the supply of one bottle of free drops.
References
2 Report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Ocular Surface 5:93-107
3 Vehof J, Kozareva D et al (2014) Prevalence and risk factors of dry eye disease in a British female cohort. BJO: epub ahead of print.
4 Schein OD, Munoz B (1997) Prevalence of dry eye amongst the elderly. Am J Ophthalmol 124(6):723-728.
5 Schein OD, Hochberg MCC et al (1999) Dry eye and dry mouth in the elderly; a population-based assessment. JAMA Int Med 159(12):1359-1363.
6 Mochizuki et al (2008) Fluorophotometric measurement of the precorneal residence time of topically applied hyaluronic acid. Br J Ophthalmol 92:108-11.
7 Snibson et al (1992) Ocular surface residence times of artificial tears solutions. Cornea 11:288-93.
8 McCann et al (2012) Effectiveness of artificial tears in the management of evaporative dry eye. Cornea 31:1-5.
9 Iester et al (2000) Improvement in the ocular surface using hypotonic ) 0.4 per cent hyaluronic acid drops in keratoconjunctivitis sicca. Eye 14:892-8.
10 Troiano et al (2008) Effect of hypotonic 0.4 per cent hyaluronic acid drops in dry eye patients: a cross-over study. Cornea 27:1126-30.
11 Aragona et al (2002) Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol 86:181-4.
12 Condon et al (1999) Double blind, randomised, placebo controlled crossover, multicentre study to determine the efficacy of 0.1 per cent (w/v) sodium hyaluronate solution (Fermavisc) on the treatment of dry eye syndrome. Br J Ophthalmol 83:1121-24.
13 Matsuo (2001) Trehalose protects corneal epithelial cells from death by drying. Br J Ophthalmol 85:610-612
14 Hill-Bator et al (2014) Trehalose-based eye drops preserve viability and functionality of cultured human corneal epithelial cells during desiccation. Biomed Research International June.
15 Chen et al (2009) Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis. Exp Eye Research 89:311-18.
16 Baudouin et al (2013) Role of hypersomolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting.
17 Aragona et al (2014) Protective effects of Trehalose on the corneal epithelial cells. The Scientific World Journal, June.
18 Luyckx J, Baudouin C. Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology. Clin Ophthalmol 2011; 5: 577-81.
Dr Rohit Narayan is an IP optometrist who runs a dry eye clinic in Nuneaton