01/03/2016
Dry eyes – what should I
recommend?
Professor Christine Purslow
PhD, MCOptom, FBCLA, FIACLE
Defining the problem
• The paradox of watery eyes?
• ‘Disorder of the tear film’?
• Often defined by our patients by their
symptoms:
– scratchy, itchy, burning, dry, sore, tired, hot,
smeary vision, excess blinking……….
– Symptoms are surprisingly reliable
IS ‘DRY EYE’ A DISEASE?
Dry eye - nuisance or a disease?
• Dry eye is a multi-factorial disease of
the tears and ocular surface that
results in symptoms of discomfort,
visual disturbance, and tear film
instability with potential damage to
the ocular surface. It is accompanied
by increased osmolarity of the tear
film and inflammation of the ocular
surface
WHAT DO DRY EYES FEEL LIKE?
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01/03/2016
What do dry eyes feel like?
•
•
•
•
•
Sore, gritty eyes
Stinging, burning
Watering eyes
Smeary vision
Irritation from air
conditioning or wind
• Red eyes and eyelids
Prevalence is ‘1 in 5’
• More than 20% adults over 45 years of age
• Rising to 30%+ in Asia
• Many more affected only under certain adverse
conditions
– ‘Episodic’ dry eye
• Probably 50% of contact lens wearers will be
affected
One of the most common eye
complaints of the elderly
HOW COMMON IS ‘DRY EYE’?
“1 in 10 British women have dry eye”
• Vehof et al, BJO 2014
•
•
•
•
•
•
4000 women of all ages
Part of the ‘twins study’ in London
1 in 10 had diagnosis of DED
1 in 5 had symptoms within last 3 months
‘New’ risk factors identified: stroke, migraine
Strong associations with: depression, pelvic
pain, irritable bowel syndrome, fibromyalgia
The burden of dry eye
• Patients with dry eyes are 3x more likely to report
problems with reading, using a computer, etc.
– Miljanovic (2007) Am J Ophthlmol 143(3):409-15
• Dry eye is linked with poor visual performance
when driving
– Deschamps et al (2013) Am J Ophthalmol 110(7):1412-9
IS IT REALLY A PROBLEM?
• QOL significantly impaired – quality of life
– Significantly reduced (Paulsen et al, 2014)
– Put on a par with having angina (Schiffman et al, 2003)
• Depression and anxiety are more prevalent in
blepharitis
– Chaing et al (2013) PLOSOne Dec
– Role for inflammation in depression
– Patel, 2013 Psychiatr Danub [Review]
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01/03/2016
Images courtesy
of David Austen
HOW DOES DRY EYE START?
Risk factors for dry eye
Mostly consistent
Suggestive
Unclear
Older age
Asian race
smoking
Female sex
antidepressants
Hispanic ethnicity*
Postmenopausal
oestrogen therapy
diuretics
alcohol
Diet low in Omega 3 or
high ratio 6:3
Beta-blockers
menopause
Antihistamines
Diabetes mellitus
acne
Refractive surgery
Low humidity
Oral contraceptives*
Vitamin A deficiency
Systemic chemotherapy
Pregnancy*
Connective tissue disease
HIV infection
Botulinum toxin injection
IBS
Ovarian dysfunction
Anxiolytics/ antipsychotics
Depression
The foundation of a good tear film
*very few reports; rest conflicting
evidence
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01/03/2016
Goblet cell distribution in conjunctiva
3 scenarios are possible with tears
• The eyes don’t produce enough tears
• The tears are poor quality
• The tears evaporate too quickly
• ‘Dry eyes don’t always appear dry!’
• ‘Quality not quantity’
Whatever the initial cause, this is what
happens next………
Common triggers for the vicious circle
Tear film
instability
Tear film
instability
Loss of microvilli
and goblet cells
Inflammation
of the ocular
surface
Excessive
evaporation from
ocular surface
Increased
osmolarity of
the tear film
Loss of microvilli
and goblet cells
Corneal surgery,
preservatives,
watery eyes
Inflammation
of the ocular
surface
Contact lenses, MGD,
blepharitis, poor diet,
dry environment, not
blinking enough
Excessive
evaporation from
ocular surface
Increased
osmolarity of
the tear film
WHAT IS THE MOST COMMON
TRIGGER FOR DRY EYES?
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01/03/2016
8 out of 10 dry
eye problems
feature
blepharitis
WHAT IS BLEPHARITIS?
Lemp et al (2012) Distribution of aqueous-deficient and evaporative dry eye in a
clinic-based patient cohort: a retrospective study. Cornea 31(5):472-8
Inflammation of the eyelids
• Blepharitis is a group of disorders which all feature
inflamed eyelid margins
• Eyelids look sore and inflamed (‘red-rimmed’ eyes)
• Two types – anterior and posterior
• Chronic condition that cannot easily be ‘cured’, but
can be controlled
Debris attached to lashes
Inflammation
Posterior Blepharitis
• Inflammation of the eye lid margin closest to the eye
• Mostly due to Meibomian Gland Dysfunction (known as MGD)
• The Meibomian Glands produce the lipids (meibum) for the
lipid layer of the tear film
• Normal meibum is clear, runny fluid, but when abnormal
becomes more solid and flow is reduced
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01/03/2016
So……..eyelids deserve more
attention than you think
From Bron et
al (2011)
Ocular Surface
9(2)
• All dry eyes need to maintain tear
volume
• Preventing excessive evaporation is
key
• ‘MGD is very likely to be the most
frequent cause of dry eye’ TFOS
2011
• LID CARE IS KEY AS WELL AS DROPS
How common is blepharitis in
Optometry?
• From people walking into optometric practice
for routine eye examinations
40%
HOW COMMON IS BLEPHARITIS, IN
GENERAL?
will show signs of MGD or blepharitis
Two studies 20 years apart show 38.9% and 47% respectively
•
Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and
treatment. Ocul Surf. 2009 Apr;7(2 Suppl):S1-S14.
•
Hom MM et al. Prevalence of Meibomian gland dysfunction. Optom Vis Sci. 1990 Sep;67(9):710-2.
FREQUENCY OF BLEPHARITIS IN A CLINIC
POPULATION
RESULTS
PREVALENCE
Eyelid
Disorder
66%
66%
Normal
34%
n=147
of incoming patients presenting with
Of course,
patients
sometimes
don’t help
themselves
…….
EYELID INFLAMMATORY DISORDERS
Dr. Benitez del Castillo (Madrid) - 1998
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01/03/2016
Put whole of my eye here
MANAGING PATIENTS WITH DRY
EYES
The influence of Essential Fatty Acids
(EFAs) on your eyelids
Management strategy
THE AIM = ‘ocular surface happy’
1. Give advice on reducing risk factors
2. Manage blepharitis and MGD
3. Lubricant eye drops (artificial tears)
**For long-standing or severe dry eyes, a combined
approach of the above may be beneficial**
• Omega 3 intake improves the secretion from
the meibomian glands (for the lipid layer of
the tear film)
• Omega 6 (GLA form) intake improves tear
secretion
• Omega 3 intake is associated with improved
cell structure on the ocular surface
Useful advice for dry eyes
WHAT ADVICE SHOULD I BE GIVING?
•
•
•
•
•
•
•
Stop smoking
Blink patterns
Taking breaks from computer
Stay hydrated
Humidity
Omega 3 intake
Control diabetes systemic medication
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01/03/2016
Looking after eyelids
• WARM
– to melt hardened meibum
secretions
• MASSAGE
– to encourage meibum to be
secreted
• CLEAN
MODERN CARE FOR EYELIDS
– to remove skin debris and
excess secretions
– to soothe inflamed lids
– to provide comfort and
freshness
The challenge of looking after MGs
Oil factories………
Hot flannels just aren’t hot enough
for long enough
• Normal meibum secretions are liquid at body
temperature
• Abnormal secretions are thicker and stiffer
• The melting point of abnormal meibum is higher
- In a normal subject starts at 32°C (Tiffany & Marsden,
1986)
WHY DON’T HOT FLANNELS WORK?
- In a patient with MGD starts at 35°C (Nagymihalyi et al,
2004; Terada et al, 2004)
- +3°C higher
(Ong & Larke, 1996)
- You need around 39-40°C for at least 5-6 mins
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01/03/2016
Warming options…
Traditional eyelid cleaning
Hot flannel
EyeBag
Blephasteam
A bit of heat…..
Dry heat
Moist Heat (ideal)
Approx £2
Approx £20
Approx £200
Variable temperature
Maintains temperature
Closely regulated
Poor compliance
Have to lie still
Can see during treatment
Unhygienic
Sterilised in microwave
hygienic
• Limited to providing some massage and
cleaning away debris of anterior
blepharitis
• Cotton pads & Baby shampoo
– Baby shampoo is a surfactant and will strip the lid
margin of debris but also the meibum
– Residue enters the tear film and leads to disruption
• Bicarbonate of Soda
– ???????
H Pult
Modern Lid hygiene
Must be kind to skin and eyes, so……..
• Avoid soap – saponification of the
meibum lipids is pro-inflammatory (and
bad for the tear film lipid layer itself)
• Avoid preservatives for the ocular surface
• Avoid perfumes and alcohol (inflamed
skin)
How frequent does eyelid cleaning
need to be?
• Twice a day for 3 weeks, then once a day onwards
How do we know this?
Independent clinical study from 2012 (Eye & Contact Lens
38(5))
• Significant improvements in symptoms and signs were
observed after 21 days of ‘intensive use’ (twice a day)
• This was sustained with ‘maintenance use’ of once a day
And then we come to topical
products……
•
•
•
•
Sprays
Artificial tears
Gels and viscous eye drops
Ointments
• How can you tell which are effective?
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01/03/2016
What you say………
“Try these drops for your dry
eyes – if they don’t bring
relief, we can try some
others”
What they hear……..
Five principles to follow when
choosing dry eye drops
“I don’t know the difference
between these products, so
here, try these and see
which one works for you.”
Effective products will interrupt this
merry-go-round at certain places……
Tear film
instability
Loss of
microvilli and
goblet cells
Protect the ocular Inflammation
surface
of the ocular
surface
Stabilise the
tear film
Manage MGD
Excessive
evaporation
from ocular
surface
Professor Christine Purslow
Head of Medical Affairs (UK & Ireland)
Thea Pharmaceuticals Ltd
So…what would you ideal drop for dry
eyes look like?





Be ‘kind’ to the ocular surface
Protect the ocular surface
Mimic the behaviour of the tear film
Provide long-lasting relief
Easy to use and apply
Increased Reduce the tonicity
osmolarity of of the tear film
the tear film
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01/03/2016
Principle 1: Avoid Preservatives
Choose Preservative Free
Avoid simple ‘goo’
Choose Hylauronic Acid
Choose Hypotonic
Choose Osmoprotective
Easy to use, economical bottle
Are all preservatives toxic?
Evaluation of the cellular viability in a Human cornea cell line after
preserved and preservative-free treatments(8).
24h
24h + 24h
72h
Control
Normal (100%) Normal (100%)
Normal (100%)
BAK 0.01%
No toxic
Viability decline (43%)
Toxic (0 %)
BAK 0.1%
Toxic (0 %)
Toxic (0 %)
Toxic (0 %)
Perborate
No toxic
No toxic
Viability decline (75%)
Polyquad
No toxic
No toxic
Viability decline (70%)
Thiomersal
No toxic
No toxic
Toxic (1 %)
Oxyd
No toxic
Viability decline (71%)
Toxic (4.5 %)
COMOD
No toxic
No toxic
No toxic
ABAK
No toxic
No toxic
No toxic
• Ocular surface inflammation in dry eye is
exacerbated by preservatives
• Epithelial toxic effects of BAK well-established,
but are dose and tear film dependent
• EDTA (disodium edetate) augments other
preservatives (& used in some non-preserved
formulations) - can irritate some
• Vanishing preservatives (sodium perborate and
sodium chlorite) might not vanish!
• TFOS experts say removing preservative is vital…..
Being phosphate-free is good
• Phosphates are often used to buffer drops
– to maintain the pH
– prevent stinging on application
• European Medicines Agency reported that (Dec
2012):
• “Cases of corneal calcification have been reported
very rarely in association with the use of phosphate
containing eye drops in some patients with
significantly damaged corneas”
• Phosphate free treatments are recommended for the safety
of ocular surface
(8) Meloni M et al. Occludin gene expression as an early in vitro sign for mild eye irritation assessment. Toxicology in vitro (2009).
Principle 2: we can do better than just
‘goo’
• Large molecule complexes added to increase
residence time
• Cellulose derivatives are water-soluble,
viscous, transparent and non-toxic
• PVA, PEG, HMC, HPC, PGMC, glycol 400
• PVA and povidone are less viscous than
cellulose derivatives
• Modern formulations are more clever………
Principle 3: choose clever key
ingredients
• Ones that mimic the tear film are termed
‘non-Newtonian’
 Hyaluronic Acid (sodium hyaluronate)
 HP-Guar
• Defy gravity
• Respond differently to force applied
• (Other attractive properties come with them)
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01/03/2016
Hyaluronic acid - key facts
HA has a prolonged residence time across the ocular
surface in comparison to other dry eye drops (1,2)
HA is superior at improving the stability of the tear film, due
to its viscoelastic properties (3)
Studies have shown that hypotonic formulations of HA eye
drops are better at relieving symptoms compared to
isotonic formulations (4,5)
Research suggests that sodium hyaluronate has a
beneficial effect on the conjunctival epithelium (6,7)
1. Mochizuki et al (2008) Fluorophotometric measurement of the precorneal residence time of topically applied hyaluronic acid. Br J Ophthalmol 92:108-11.
2. Snibson et al (1992) Ocular surface residence times of artificial tears solutions. Cornea 11:288-93.
3. McCann et al (2012) Effectiveness of artificial tears in the management of evaporative dry eye. Cornea 31:1-5.
4. Iester et al (2000) Improvement in the ocular surface using hypotonic ) 0.4% hyaluronic acid drops in keratoconjunctivitis sicca. Eye 14:892-8.
5. Troiano et al (2008) Effect of hypotonic 0.4% hyaluronic acid drops in dry eye patients: a cross-over study. Cornea 27:1126-30.
6. 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.
7. Condon et al (1999) Double blind, randomised, placebo controlled crossover, multicentre study to determine the efficacy of 0.1% (w/v) sodium
hyaluronate solution (Fermavisc) on the treatment of dry eye syndrome. Br J Ophthalmol 83:1121-24.
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Principle 5: help the patient comply
• Even the best ingredient delivered in a poor bottle
will be ineffective
• Eye drop bottles are notorious for being hard to use,
especially generics
• Clicker/popper systems might seem OK in a young
hand but not always so good in an older one
Principle 4: protect the ocular surface
• We can choose products that protect against high
osmolarity:
– Hypotonic formulations to rebalance tonicity
• Hyabak, Theratears, Oxyal, Artelac Rebalance
– Osmoprotective formulations
• Optive, Thealoz, Thealoz Duo
• We have products that protect against
desiccation and slow cell death
– Thealoz: contains Trehalose, a disaccharide with
unique properties
Choose Preservative Free
Avoid simple ‘goo’
Choose Hylauronic Acid
Choose Hypotonic
Choose Osmoprotective
Easy to use, economical bottle
Thank you for listening
[email protected]
THANK YOU FOR LISTENING
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