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Back to the Future II: Diagnosis and
Management of Dry Eye
THIS COURSE EXPIRED ON 30 NOVEMBER 2016 | 26 February 2016
By Dr. Margaret Lam
The 2007 Dry Eye Workshop (DEWS) Report emphasises
that it is important to adopt a logical stepwise approach to
grading the severity of dry eye in an effort to determine
appropriately staged prescribing and management.
This article is a summary of the DEWS Report findings for optometrists in clinical practice. In
true Back to the Future style, it also travels forward to explore emerging dry eye
management strategies that may be beneficial to optometrists in practice.
Additionally, this article continues on from the education article entitled Back to the Future,
the Dry Eye Workshop Report that appeared in the June edition of mivision.
Dry eye causes are multifactorial, and the severity of dry eye can be accurately graded by
putting due consideration into both patient symptoms and clinical signs. We can thus
determine a severity level and prescribe appropriate management tailored to address each
fundamental cause.
Level One Dry Eye
• Mild to minimal ocular symptoms
• Mild or minimal ocular signs such as conjunctival injection, conjunctival staining, and
corneal staining
• Tear volume normal
• MGD status variable
• TFBUT and Schirmer results may appear normal (10-15 seconds)
Level One Management
•
•
•
•
Education and environmental/dietary modifications
Elimination of offending systemic medications
Artificial tear supplements, gels and ointments
Eyelid therapy
Education
As eyecare practitioners, we are familiar with educating patients about dry eye. When
explaining dry eye disease, patients usually gain a reasonable understanding of their
condition, however most patients choose to follow only some of the treatments prescribed by
the eyecare practitioner. This becomes a source of frustration for both patient and
practitioner, because dry eye usually has a number of causes, and if all causes are not
addressed, patient symptoms persist with little significant improvement.
To motivate a patient to follow all the treatments recommended it is helpful to educate them
with a greater understanding of the overall mechanism of how the eye works in
remoisturising the ocular surface. There are numerous online youtube resources that outline
meibomian gland dysfunction that can serve as a good platform for your explanation. The
crux of getting patients motivated to comply with all recommendations is getting them to
understand the complex but interconnected mechanism for dry eye. Patients are much more
motivated to address all causes when they understand that dryness causes subsequent
inflammation, the inflammation causes further dry eye, and without intervention, the condition
may continue to escalate.
It is helpful to explain this to the patient at an appropriate time and with a personalised
approach. The explanation that would be appropriate for a fellow colleague in the health or
medical profession, or a patient that has thoroughly researched dry eye, would be completely
different to a patient who is unfamiliar with dry eye and is lost about their symptoms.
A useful analogy may be that of dry eye being similar to a ‘dry windscreen wiper scraping
over the surface of a car windscreen’. When meibomian gland dysfunction occurs, this
analogy can describe insufficient lipid reaching the ocular tear film and causing the
evaporative effects of aqueous deficiency, that is, the lack of sufficient moisture causing the
symptoms of the initial discomfort. The dry windscreen wipers ‘scraping’ mechanism of the lid
wiper over the surface of the eye can be described as though it has a frictional component
due to the aqueous deficiency, which causes the subsequent inflammatory conditions that
develop. Although simplified, this helps patients to understand that it is necessary to address
all the issues that are causing their dry eye, rather than handpicking a few treatments from
those prescribed for them.
Educating patients to ‘think blink’ and to perform full blinks is also useful, particularly when
they are in front of environmental stressors such as computer screens and tablets. Some dry
eye sufferers that present with little to no SPK may be disguising far more obvious clinical
signs of corneal SPK by doing very frequent partial blinks.
Environmental and Dietary Modifications
Environmental modifications to reduce or avoid exposure to known triggers may reduce dry
eye symptoms. Also helpful is prescribing prophylactic measures that can prelubricate the
eyes prior to encountering environmental situations that usually trigger dry eye symptoms.
A key essential proactive measure is to ensure sufficient omega-3 is in the dry eye patient’s
diet. The typical western diet has 20-25 times more omega-6 than omega-3, and omega-6 is
a precursor for Arachidonic acid and other proinflammatory lipid mediators. Omega-3 is
essential for the opposite effect, as it causes an inhibitory effect of these mediators.
1
An
Omega-3 supplement, taken orally twice a day, has been shown to bring significant
improvement in patient symptoms, as well as their ocular surface and conjunctival staining.
2
Other dietary modifications include changing medication that may induce adverse effects of
dryness. Although many medications may produce this effect and need to be looked at
individually, common culprits are the anticholinergics such as the antihistamines and
antidepressants.
Elimination of eyedrops that may contain preservatives may also make a considerable
difference.
Examples of topical eyedrops that may exacerbate ocular surface disorders are topical
antihypertensive agents for glaucoma that use benzalkonium chloride as a preservative.
Benzalkonium chloride, as has been established, is a preservative that is particularly known
to have a deleterious effect on epithelial cells and the ocular surface.
3
Approximately 40 per
cent of patients who are on glaucoma medication have ocular surface disorder (OSD)
issues.
4,5
Prescribing alternative preservative free options where possible will lessen ocular
adverse effects on the precorneal tear film, the cornea and conjunctiva associated with
OSD.
6
Artificial Tear Substitutes, Gels and Ointments
As touched on in the first article, the cornerstone of dry eye management starts with effective
lubrication of the ocular surface. This can reduce the symptoms for dry eye development,
and furthermore, may potentially reduce its subsequent inflammatory effects by diluting the
hyperosmolarity of the ocular tear film. By doing so, it reduces the subsequent damage to the
ocular surface.
‘Artificial tear substitutes’ may be thought to be quite inappropriately named, as the ‘artificial
tears’ of lubricating eye drops do not mimic the composition of normal tears. A more
appropriate name would be an ocular lubricant as their main action is to provide a lubricating
action on the ocular surface.
There are few large scale studies that exist to compare the efficacy and performance of
certain eye lubricants against others, however, some lubricants certainly perform better than
others.
7
Some lubricants worth specific mention have unique properties, or are closer to the
composition of natural tears than others.
One of those is Theratears, which mimics the electrolyte composition of human tears.
Another is Systane drops, which contain the gel-like HP-Guar that demonstrates preferential
binding to the more hydrophobic, desiccated or damaged areas of the surface epithelial cells,
the thought being that they provide temporary protection for these cells.
8,9
Additionally, Systane lubricating drops and Optrex liposomal sprays contain both lubricating
and lipid components.
10
It has been established that an increased thickness in the lipid layer
contributes significantly to tear film stability, demonstrated in the Systane lubricating drops
and Optrex liposomal sprays.
Although both increase lipid layer thickness and lead to increased tear film stability, more
recent studies show that liposomal sprays compare favourably against lubricating drops in
reducing clinical signs of dry eye such as staining with lid parallel conjunctival folds
(LIPCOF), lid margin inflammation and improvements in invasive tear break up time
(TBUT).
11,12,13,14,15
An appropriate regimen of lubrication will usually include night time application of an
ointment or gel. Fortunately, most ointments and gels are preservative free as they do not
support bacterial growth.
16
Eyelid Therapy
Eyelid therapy comprises two parts, firstly, treatment for anterior blepharitis by antiinflammatory interventions such as lid cleansing wipes or cleansing foams.
Secondly, meibomian gland dysfunction (MGD) is implicated in 80 per cent of dry eye cases,
so eyelid therapy to address posterior blepharitis and MGD thus also comprises hot
compresses and meibomian gland expression, and is an important part directed at managing
these conditions.
As we know from the DEWS Report, the meibum of a non dry eye sufferer appears clearer
and more easily expressed, and in contrast, those with MGD related dry eye will have
increasingly thicker, waxier meibum that is harder to express. Cases with severe dry eye
thus require a higher temperature to melt meibum effectively, compared to normal patients.
Consequently, the worse the severity of MGD, the less improvement they see with an athome regimen of hot compresses. In practice, this means the worse the MGD-related dry
eye, the less likely they will find hot compresses effective, and thus the worse the motivation
to continue to comply.
Tomlinson reported that patients that have four or more functioning meibomian glands that
are expressible are far less likely to have dry eye symptoms.
17
Similar findings from Bron and
Tiffany showed that as long as there are still sufficient glands present, and the patient has
addressed any aqueous production issues, treatment targeted to address MGD can be
beneficial for reduction in dry eye.
18
In-office therapy for meibomian gland expression can be easily introduced in general
optometric practice. The use of an in-office lid warming device such as a Blephasteam
device can deliver more consistent heat compared to a hot compress, thus improving
compliance. Blephasteam dry eye treatment warms the eye to the appropriate temperature
to melt meibum and then a Mastrota paddle can be employed to express the meibomian
glands. Many studies show that Blephasteam is useful and safe as a lid warming device,
19,20
and manual expression following this can be effective by improving the meibum quality
21
and
thus increasing the TBUT to normal levels.
22
A study by Doan et al. that looked at the efficacy
of this combined technique has shown it produces promising results for considerable
reduction in symptoms in those with MGD-related dry eye.
23
Level Two Dry Eye
• Moderate ocular symptoms
• Moderate ocular signs of conjunctival injection, conjunctival staining but no corneal staining
• Reduced tear volume, slight debris appearing in tear film
• MGD status variable
• TFBUT and Schirmer results 10 seconds or less
Level Two Management
If level one treatment is inadequate for the management of symptoms, the addition of
management guidelines for level two is required:
• Anti-inflammatories
• Secretagogues
• Tetracyclines (for meibomianitis and rosacea)
• Punctal plugs
• Moisture chamber spectacles
Anti-Inflammatories
Topical corticosteroids and cyclosporine-A (cSA) are well-established anti-inflammatory
therapies useful in dry eye management.
24,25,26,27,28,29,30,31,32
There is a range of studied topical steroid concentrations discussed in DEWS, but a good
‘recipe’ finding success with practitioners is to prescribe the topical non-preserved
corticosteroid prednisolone 0.5 per cent minims for two weeks, four times a day, with an
appropriate taper, provided any contraindications have been excluded, including any active
ocular infection, particularly epithelial herpetic simplex keratitis, pregnancy or breastfeeding.
Although adverse effects are somewhat rare, and have only been reported from prolonged
usage, the risk for posterior subcapsular cataract development, ocular hypertension and
glaucoma should also be considered for any particular patient.
33
In moderate to severe dry eye, topical cyclosporine-A concentrations found to be most
appropriate were 0.05 per cent and 0.1 per cent. In Australia, with no commercial access to
restasis, these must be specially compounded or requested via Special Access Scheme.
Gunduz et al. found that topical cyclosporine-A 0.05 per cent applied twice daily for three
months produced the most significant reduction in patient symptoms, and 0.1 per cent
produced the most significant reduction in objective measurements such as corneal
staining.
34
Contraindications that need to be ruled out before prescribing topical cyclosporineA include pregnancy, breastfeeding mothers, and children under 16, where its use has not
been studied.
Since DEWS, for recalcitrant cases that show a suboptimal response to corticosteroids or
cyclosporine-A treatment separately, there have been favorable reports for concurrently
prescribing both. Byun et al. reported faster symptom relief and improvement in ocular signs
with the combined use of prednisolone acetate 1 per cent and cyclosporine-A 0.05 per cent
prescribed for the first three weeks, followed by cyclosporine-A only for the duration of three
months. There is reported to be faster symptom relief and improvement in ocular symptoms,
TBUT, Schirmer’s and ocular staining with this intervention for patients compared to the use
of topical corticosteroids alone.
35
However, in this study, Byun et al. used prednisolone
acetate which contains benzalkonium chloride as a preservative. In practice, the use of non
preserved minims of prednisolone 0.05 per cent should be considered in its place.
Intensive application of an appropriate lubricant is essential with all of these options. This is
to ensure the tear film has sufficient lipid and aqueous components. Lubricants such as
Systane balance or a liposomal spray such as Optrex is essential in establishing a thick lipid
layer to reduce dry eyes due to MGD.
As dry eye has ‘predictable unpredictability’, cessation of symptoms may occur as a result of
these interventions, but may recur in future. Re-prescribing these again as a pulse dose
added to the patient’s normal dry eye regimen should be considered when required.
In terms of other significant anti-inflammatories since DEWS, medihoney deserves strong
mention. The anti-inflammatory and anti-bacterial effects of honey have been well
established for recalcitrant wounds that have been non-responsive to antibiotic therapy.
39
A study by Albietz et al, into the ocular flora levels of those with tear deficiency and MGD,
established significantly higher levels of bacterial flora which potentially contributed to tear
film instability and ocular surface degradation. Honey is hygroscopic, meaning that it draws
moisture out of the environment and thus dehydrates bacteria to stifle its ability to produce
colony forming units. Medihoney applied topically three times a day brought ocular flora
levels down to the levels found in non-dry eye sufferers. This was found universally in
subgroups with Sjogren syndrome tear deficiency, non Sjogren tear deficiency, and MGD.
37
In practice, patients need to be forewarned there will be considerable stinging on application
of medihoney due to its low pH. When employed as a treatment regimen, practitioners have
found twice daily application or even once daily application at night time may be sufficient to
produce similar effects in the reduction of ocular symptoms. Instillation of an ointment prior to
medihoney can reduce the sting patients observe on application.
Secretagogues
Secretagogues are topical pharmacological agents that increase production of aqueous and
mucous secretion to contribute to the ocular tear film, such as diquafosol tetrasodium,
hydroxyeicosatetraenoic acid, rebamipide, gefarnate, ecabet sodium and 15(S)-HETE.
38
These are not commonly encountered in general optometry practice but studies show some
promise in their effectiveness.
Tetracyclines
Oral tetracycline derivatives, such as minocycline and doxycycline, have desirable antibacterial and antimicrobial effects that have been well established for their use in dry eye
management.
39,40,41
Being antimicrobials, they decrease bacterial flora that produces
enzymes that break down lipids and also inhibit lipase production.
42
In doing so, they are
thought to contribute to higher lipid levels in the ocular tear film. Tetracyclines also inhibit
matrix metalloproteinase (MMP) expression, particularly MMP-9, a cytokine that is a known
proinflammatory cellular mediator in elevated levels in those with dry eye. Dry eye related to
ocular rosacea is particularly responsive to doxycycline.
43,44
For MGD related dry eye, consider co-managing with a general practitioner or
ophthalmologist to prescribe a course of oral doxycycline. There is no consensus on an
exact dosage for doxycycline,
45
so a guideline or ‘recipe’ of oral doxycycline 50mg taken
twice daily for two weeks, followed by a dosage adjustment of 25mg once daily to be
prescribed following the higher dosage over the following six months. Note that the dosage
described is the anti-inflammatory dosage and half that of the usual antibacterial dosage for
the treatment of infection.
Contraindications health care practitioners should be mindful of when considering prescribing
oral tetracycline derivatives, include women who are pregnant as they cross the placental
barrier; and children under eight years of age, as they have effects of permanent
discolouration of teeth, and have effects on foetal toxicity and skeletal development.
46
Potential adverse effects include gastrointestinal upset, photosensitivity, possible renal
impairment, and overgrowth of usually non-susceptible organisms such as fungi to cause
vaginal candidiasis.
47
All health care practitioners, regardless of setting, should be mindful of carefully prescribing
oral tetracycline derivatives for women of childbearing age because of the effects on foetal
development.
With regard to patients with MGD related dry eye, Kashkouli et al. recently published a study
that shows a one week course of Azithromycin taken orally for 500mg for day 1, and 250mg
taken once daily for day two to five, has better results than a prolonged course of
doxycycline in terms of clinical signs of improvement, patient symptoms, and less reported
adverse effects of gastrointestinal upset compared to doxycycline.
48
As the results of this
study become more widely known, a larger number of practitioners will be likely to be
prescribing it in place of doxycycline.
Punctal Plugs
Punctal plugs can be very beneficial in certain circumstances, the rationale being that in
those with a wide range of aqueous deficient dry eye groups, plugs can reduce tear
clearance and increase tear volume. This is particularly appropriate once any active ocular
surface inflammation has been resolved.
Temporary plugs can be inserted to assess efficacy before a more permanent solution is
offered and to minimise maintenance. Although plug extrusion is an issue in up to 50 per
cent of cases with certain plug types, the issues are minor; being the expense and
inconvenience of having to have the plug reinserted. Complications are rare but worthwhile
being educated about, including internal migration of the plug down the nasolacrimal duct
requiring surgical removal, biofilm formation, infection and granuloma formation around the
plug.
49
In practice, considerable improvement in symptoms has been seen with punctal plugs.
Moisture Chamber Spectacles
The most rational theory behind the effectiveness of moisture chamber spectacles has been
proposed by Korb et al. around increasing periocular humidity to increase the lipid layer in
the ocular tear film, so these can be helpful for those at a level with moderate to severe dry
eye.
1
Level Three Dry Eye
• Severe ocular symptoms
• Severe signs of conjunctival staining and severe conjunctival injection
• Corneal staining present
• Tear film filamentary keratitis and mucus clumps in tear film
• MGD involvement
• TFBUT five seconds or less and Schirmer test 5mm/min or less.
Level three Management
If level two treatment is inadequate for the management of symptoms, the addition of
management guidelines for level three is required:
• Serum – autologous serum
• Contact lenses
• Permanent punctal occlusion.
Level Four Dry Eye
• Severe and disabling ocular symptoms
• Severe signs of conjunctival staining and conjunctival hyperemia
• Corneal staining present in the form of severe SPK
• Tear film shows filamentary keratitis and mucus clumps in tear film
• MGD involvement but now severe enough to cause remodeling of the lid margins, such as
keratinization of the lid margins, symblepharon and trichiasis
• TFBUT zero seconds and Schirmer test 2mm/min or less.
Level Four Management
If level three treatment is inadequate for the management of symptoms, the addition of
management guidelines for level four is required:
• Systemic anti-inflammatory medications
• Surgery-tarsorraphy, amniotic membrane transplant, salivary gland transplant, or mucus
membrane surgery.
What has come since the DEWS Report – IPI and Lipiflow
Intense Pulse Light therapy (IPL) and Lipiflow therapy is worth mentioning. While Lipiflow
has been available for a few years and has received mixed feedback from patients for dry
eye treatment, recent double masked studies presented by Assoc. Professor Jennifer Craig
on IPL show promising results in dry eye cases with symptomatic MGD. IPL is worthwhile
discussing, but beyond the scope of this article on dry eye management in the general
optometric practice.
There are other areas of dry eye treatment that could not be covered in this article, such as
the use of contact lenses, which can provide a considerable and meaningful improvement to
quality of life for patients with severe dry eye.
Where are We Now?
The DEWS Report has provided us with an excellent guide to management and a treatment
strategy based on stages to match the level of classification of severity.
However, to quote the words of Doc Brown from Back to the Future fame when speaking
about the time travelling Delorean, ‘If my calculations are correct, when this baby hits 88
miles per hour, we are gonna see some serious sh*t…’
Unfortunately, when it comes to dry eye management, although we have figured out how our
flux capacitor works, and we’ve worked out a few key elements that we know may placate
dry eye, we haven’t mastered the art of time travel or gotten our Delorean to 88 miles per
hour… we are yet to reach a ‘future’ where there is a solution for dry eye.
I am optimistic that it is just a matter of time when, by better understanding the inflammatory
pathways, we will be able to offer treatment that effectively reduces and better controls the
symptoms and existence of dry eye disease.
I like the following statement that hides like a gem deep within the volumes that is the DEWS
Report: ‘The foremost objectives in caring for patients with dry eye disease are to improve
the patient’s ocular comfort and quality of life, and to return the ocular surface and tear film to
the normal homeostatic state. Although symptoms can rarely be eliminated, they can often
be improved, leading to an improvement in the quality of life.’
Cue the lightning spark to ignite the Delorean to bring the eventual solution for our dry eye
patients? I refer to the Back to the Future movie sequels that were better than the original.
The passage of time since the DEWS Report was first published in 2007 means the Tear
Film and Ocular Surface Society has started work on their sequel, the DEWS Report II – an
assessment of current research, expansion of emerging treatments and update on findings
that have come out since the first DEWS.
The steering committee plans to start mid 2015 to critically assess the etiology, mechanism,
distribution and global impact of dry eye, and provide an update on management and
therapy. There is talk the very definition of dry eye as we know it will also be fundamentally
changed.51
Doc Brown, confidently says, ‘Where we’re going, we don’t need roads’. But that just reminds
me of the perpetual male/female disagreement that surrounds reading maps, and so I beg to
differ. Take out that damn map and get directions! We’ll get there faster and more reliably!
Ideally, where we are going in the future, the focus needs to be less on a ‘cure’ for dry eye
and more on effective management… realising that the original DEWS Report and no doubt
DEWS Report II will provide us with an excellent roadmap to take us in the correct direction.
In the meantime, We Keep Calm, And Start the Dolorean. Best wishes for your success
when managing dry eye patients in practice.
Margaret Lam BOptom
UNSW, OA, CCLSA, OSO,
IAO graduated from the
University of New South
Wales in 2001. A principal of
theeyecarecompany she
practices full scope
optometry and has extensive
experience in specialty
contact lens fitting in corneal
ectasia, keratoconus and
orthokeratology.
Ms. Lam has been a past
recipient of the Neville
Fulthorpe Award for Clinical
Excellence. She currently
serves as the State President
of the Cornea and Contact
Lens Society of Australia for
NSW (CCLSA).
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