Dry Eye 2018

and
present...
Dry Eye 2018
An update on dry eye research from
New Zealand, Australia and further afield
• TFOS DEWS II - a year on • Blinking and the tear film • Cataract surgery and dry eye
• Ocular allergy and dry eye • Dry eye and autologous serum
• Not all eye drops are created equal • So you want to set up a dry eye clinic?
• And much, much more…

26
Contents
DRY EYE 2018
17 A year on from TFOS DEWS II
30 Cataract surgery and dry eye
34 Dry eye and autologous serum
40 Setting up a dry eye clinic
22
33
38
29

DRY EYE 2018
Dry eye in practice By
Lesley Springall, editor NZ Optics
SINCE OUR LAST dry eye special feature,
dry eye has gone mainstream. My in-box
never empties of news about the latest dry
eye products and dry eye research or different
organisations offering the next best thing for dry
eye sufferers. Spurred on by the hard-working TFOS DEWS II team and
the multitude of international ambassadors who have come to the
organisation’s aid to champion dry eye in their region (see main story,
this page), dry eye is finally beginning to get the attention it deserves.
Since the TFOS DEWS II report was released last year, there’s been a
plethora of research started, completed and ongoing; a great deal more
sharing of ideas; and a far greater focus on dry eye from across the eye
health spectrum, all of which can only be good for patients whose lives
are often severely affected by the pain and discomfort of dry eye disease.
We are proud to bring you the latest update on all things dry eye from
this part of the world and further afield, recognising the collaborative
efforts ongoing in dry eye today, many initiated or involving our own
University of Auckland.
We would like to thank the many contributors to this year’s Dry Eye
Special Feature, but especially our clinical editor, Associate Professor
Jennifer Craig, New Zealand’s own international dry eye expert who,
with considerable time and effort on her part, makes this feature
possible. Jennifer not only helps us celebrate the work on dry eye on
this side of the world, but also ensures the quality and breadth of the
dry eye research and news we share continues to further all of our
understanding and knowledge of dry eye.
TFOS DEWS II:
a year on…
By A/Prof Jennifer Craig, vice-chair, TFOS DEWS II
IT’S BEEN A full year since the outcomes of the Tear Film & Ocular
Surface Society’s second Dry Eye Workshop (now better known as TFOS
DEWS II) were released to the world in a series of 10 reports that distilled
the scientific evidence and provided an updated global consensus view on
various aspects of dry eye… and what a year it’s been!
Whether it was greater public awareness; increased recognition of
the impact dry eye has on quality of life; a sense of optimism that there
are more available therapeutic options than ever to make a difference
to affected patients’ lives; or simply a lack of patience to see the longpromised
outcomes of the two and a half years’ of effort by more than
150 experts, I’m not sure, but the results were certainly eagerly awaited by
YOUR VISION. OUR FOCUS.
researchers, clinicians, industry, regulators and patients alike.
Ensuring outcomes reach those who matter
A year on, as I pack for the third Ocular Surface and Keratoprosthesis
Topcon SL-D701
Conference (OSKON) in Chennai, India - the most recent area in the
Topcon’s premium digital ready Slit Lamp with tower style illumination column.
world in which TFOS DEWS II is being Homogeneous showcased LED illumination - there’s Optional been enhanced little filter sign
system for Meibomian
5-step magnification up to 40x
of this initial interest dwindling. Practitioners across the world gland observation remain and Superior
14mm Slit illumination
Fluorescein observation
eager to improve their understanding DC-4 Digital of dry Camera option eye disease (DED), learn
more about the key outcomes from the report and update their practices
accordingly to provide the best service possible to their patients.
Topcon CV-5000
It’s been pleasing to see entire international conference sessions devoted
Computerised Vision Tester - optional integration with PC-50s LCD Visual Acuity Chart.
to the presentation
Automated Refractor
of the
Head controlled
TFOS
by KB-50
DEWS
colour touch
II
screen
reports.
& dial controller
The first such sessions
Advanced integration – pull through previous script and/or auto-refraction. Export final
were at the TFOS conference in Montpellier, ARVO in Baltimore and
subjective data to practice management software
in Washington DC in 2017. In Washington, interest was so keen, the
interactive presentations were live-streamed to other countries. Interest
has continued to spread and I’ve Topcon had the TRK-2P opportunity to present TFOS
DEWS II sessions, in person, at conferences Completely automated alignment, as far focus afield and measurement as Romania acquisition.Flexible (Sibiu,
colour
touch-screen for versatile positioning. Integration with Practice Management Software.
Transylvania), India (Chennai), and All four measurements, Peru (Lima) in both eyes, as in less well than 60 as seconds! to ensure
Auto-Refraction
Auto-Keratometry
that our new found dry eye knowledge
Non-contact
is passed
Tonometry
on more locally
Non-contact
in
Pachymetry
New
Zealand. I’ve also had the pleasure of contributing to a sponsored Canadawide
tour, an initiative designed to take TFOS DEWS II to Canadian
optometrists throughout the country, beyond just the main centres.
We’ve tried to maximise the relevance of the workshop’s outcomes to
clinicians in optometric practice, so a practical format to the presentations
has been adopted. A conventional slide presentation has been supplemented
with a relatable, live demonstration of the recommended TFOS DEWS
II dry eye diagnostic process, including examples of how appropriate
therapeutic strategies might be applied. This has been very well-received by
practitioners around the world who report having made changes to their
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implemented in a clinical setting.
An example of this live demonstration teaching format can be viewed
A/Prof Jennifer Craig in Lima flanked by TFOS’ A/Prof David Sullivan and Prof James Wolffsohn
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• Includes Meibomian Gland imaging, tear film breakup time,
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WWW.EYEONOPTICS.CO.NZ | 17

DRY EYE 2018
from the first TFOS DEWS II presentation of this kind I delivered along with
Professor James Wolffsohn (UK) and Professor Lyndon Jones (Canada).
This was recorded by the British Contact Lens Association (BCLA) at
their conference in June 2017 and is freely available at www.tearfilm.org/
dettconferences-tfos_dews_ii_live_presentations/5857_5581/eng/.
Attempts have been made to address different practitioner learning
styles and opportunities by providing the material in multiple formats:
editorials and continuing education articles as well as podcasts and online
CPD. Moderating an online CPD session for international online medical
information provider Medscape was a novel experience (see picture).
Encouraging education and discussion…
Supplementing the recommendations from the report, TFOS has
further sponsored the creation of nine educational videos on diagnostic
techniques – tear film stability assessment and evaluation of ocular
surface staining, including lid margin staining , amongst others - www.
tearfilm.org/dettconferences-diagnostic_videos/5582_5581/eng/ - as well
as five videos on recommended management strategies, covering a range
of therapies from lid hygiene to punctal plugging - www.tearfilm.org/
dettconferences-therapeutic_treatment_videos/5583_5581/eng/. These
have been designed to encourage global consistency in technique and are
suitable for use by practitioners who wish to expand their skills in dry eye
or brush-up on existing skills and students learning the techniques for the
first time.
Getting the word out to all those who might benefit was always a major
goal of TFOS DEWS II. As a result, and thanks to industry sponsorship,
the executive summary and in some cases, the entire report (close to 400
pages) have been, or are in the process of being, translated into multiple
languages, including French, Italian, German, Spanish (sponsored by
Allergan), Chinese, Korean, Portuguese, Vietnamese (sponsored by
Novartis), Romanian, and Turkish (sponsored by SIFI). In addition, a
more layman’s version of the executive summary has been written for
English-speaking patients to encourage awareness and understanding of
Add data to your insights.
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can help guide your diagnosis and management of the ocular surface.
In fact, the point-of-care TearLab Diagnostic Test provides precise
and predictive information regarding tear osmolarity, an important
biomarker of ocular surface health.
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A/Prof Craig moderating Medscape’s online CPD session
the disease amongst those directly affected. This is currently also being
considered for translation into other languages.
…and further research and awareness
The report continues to help increase awareness and recently has been
used in an attempt to encourage better government funding in the US
for dry eye research. In July 2018, TFOS and the Alliance for Eye and
Vision Research (AEVR) joined with the vision community and coalition
partners (including major US stakeholders in eye care and research such as
ARVO and the American Academies of Optometry and Ophthalmology)
to attend a Congressional Briefing and delegation visits on Capitol Hill
in Washington DC. This was the second year that the Dry Eye Awareness
Month of July has been recognised in this way. The Briefing focused on
TFOS DEWS II and its impact on clinical practice and research.
Recognising that the work of TFOS is not possible without the help
of many people, TFOS has appointed ambassadors across the world to
facilitate the dissemination of ocular surface knowledge gained through
TFOS DEWS II. I’m honoured to have been appointed the ambassador for
New Zealand while Dr Maria Markoulli and Dr Laura Downie serve as
the ambassadors for Australia. So, if you’re aware of an unmet need where
TFOS might be able to assist, be sure to let us know.
Where to next – creating benchmarks
One of the major gaps in knowledge identified by TFOS DEWS II was the
management of different subtypes and severities of DED. Certainly, we
no longer expect all patients to achieve adequate resolution of symptoms
from aqueous tear supplementation alone, but as we introduce a range
of therapies to manage lid disease as well as lacrimal gland insufficiency,
TFOS DEWS II recognises there’s a need for better evidence regarding
which therapies will best suit which patients and at which point in their
disease. As a starting point, a survey, to which many New Zealand clinicians
contributed, has been conducted. Once analysed, the outcomes will
describe how practitioners in different parts of the world are diagnosing
and managing dry eye to provide a benchmark of standard of care and to
highlight areas where scientific evidence is lacking and where adequately
masked, randomised and controlled clinical trials should be conducted.
Understanding the natural history of DED
Another gap to be filled is in better understanding the natural history
of DED and its common cause, meibomian gland dysfunction. To that
end, through collaborations at Aston University in the UK with Professor
James Wolffsohn, I was able to participate in the Royal Society’s Summer
Science Symposium in London in early July. Members of the public who
visited the seven-day exhibition, were offered an opportunity to learn
about dry eye and to contribute to the research. This resulted in more
than 1750 individuals providing data on their demographics, symptoms
and comfortable staring capabilities (see p26), and around 1400 of those
undergoing a rapid dry eye workup on the Oculus Keratograph 5M.
This initiative has generated a wealth of data which it is anticipated will
contribute to our understanding of how commonly dry eye occurs and
offer insights into its relationship with age, sex and other risk factors.
Associate Professor Jennifer Craig is head of the Ocular Surface Laboratory at the
University of Auckland, was vice-chair of TFOS DEWS II and is clinical editor of NZ Optics’
annual special feature on dry eye.
18 | NEW ZEALAND OPTICS SEPTEMBER 2018

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DRY EYE 2018
Ocular Surface Laboratory update
By A/Prof Jennifer Craig, head of OSL
OVER THE YEAR there’s been
a strong team of individuals
working under the Ocular Surface
Laboratory (OSL) banner.
We’ve had some fantastic
research support on the latest stage
of our exploratory work on manuka
honey as a treatment for blepharitis
(www.eyeonoptics.co.nz/articles/
archive/honey-for-blepharitis/)
from part-time research fellow Dr
Andrea Cruzat, who joined us from
Schepens Eye Institute in Boston.
A difficult career choice required
Andrea to relocate to Chile recently,
sadly, but we plan to continue our
collaborations and hope to work
together again in future. Helping
to soften the blow of Andrea’s
departure, we’ve been delighted to
welcome clinician scientist and full-time research fellow, Dr Alex Muntz,
who joins us from the University of Waterloo where he completed his PhD
under the supervision of Professor Lyndon Jones. His article in this special
feature describes the research he’s been involved in, evaluating the eyelid
margin at a cellular level.
The lab supports a large number of research students who work
diligently to complete degrees at doctoral, masters and honours level,
or join us for shorter-term projects for medical programme selectives,
research electives or as summer students. It’s exciting to see senior PhD
students, Sanjay Marasini and Ally Xue, close to completion of their PhD
studies, and we were delighted to see Dr Priyanka Agarwal, who was
supervised by Dr Ilva Rupenthal and myself, successfully defend her PhD
thesis recently and receive the honour of placement on the Dean’s list of
Excellence.
We also welcome Dr Michael Wang as the newest PhD candidate in
the group. His project will focus largely on epidemiological studies of
dry eye, but his extensive experience in the tear film and ocular surface,
from his collaboration with the lab over many years, will no doubt see
his involvement across many other areas during this time. Doctoral cosupervision
opportunities extend as far as Melbourne where second-year
PhD student, Ceecee Zhang (University of Auckland optometry graduate)
is exploring the neurotrophic potential of omega-3 in a study in diabetes,
under the primary supervision of senior lecturer, Dr Laura Downie.
BOptom honours students Lexia Ah Kit, Brinda Mamidi, Alicia Han and
Kylie Mann completed projects with us last year, some published examples
of which are described below.
We were delighted to have optometrist and now junior doctor Dr
William Shew, return to the OSL to conduct a repeatability evaluation
of infrared meibography and to work with Dr Simon Dean, Dr Kosar
Kheirabi and the team, on projects evaluating the impact of chalazion
surgery on the meibomian glands, in collaboration with Dr Brian Sloan,
Olga Brochner and Kathryn Lee at Auckland Hospital. Results of this
work are currently in preparation for publication, after which we hope to
share the outcomes in a future issue of NZ Optics.
Publishing more than 20 articles in peer-reviewed scientific optometry
and ophthalmology literature last year alone, the OSL was a veritable
hive of industry and all credit goes to those who worked hard to get these
papers to this level.
During the year, our team focused on three main dry eye disease
research areas including studies relating to its epidemiology and
diagnostic test refinement as well as clinical trials that seek, through
clinical and laboratory testing, to evaluate the outcomes of the increasing
number of therapeutic and management strategies. The following articles
(entitled OSL) provide an overview of some of the recently published
projects from the OSL team in each of these three areas.
The Ocular Surface Laboratory (OSL) is a research facility located within the
Department of Ophthalmology at the University of Auckland. Led by A/Prof Jennifer
Craig, a team of clinical researchers contribute to the better understanding of ocular
surface disease to improve patient management of anterior segment disorders and, in
particular, dry eye disease.
20 | NEW ZEALAND OPTICS SEPTEMBER 2018

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DRY EYE 2018
OSL: Blinking
and the tear film
By Dr Michael Wang, Leslie Tien, Alicia Han, Jung Min Lee, Dabin Kim, A/Prof Jennifer
Craig (Auckland) and Dr Maria Markoulli (Sydney)
ALTHOUGH BLINKING TRAINING is
commonly recommended as part of the multimodal
management of dry eye disease, the
relationship between clinical measurements
of blinking patterns and markers of dry eye
severity remains yet to be established. The
influence of blinking patterns on tear film
parameters, ocular surface characteristics
and dry eye symptomology was therefore
explored in a recently published age, gender
and ethnicity-matched cross-sectional study 1 ,
conducted by the University of Auckland Ocular
Surface Laboratory (OSL), in collaboration with
senior lecturer Dr Maria Markoulli from the
School of Optometry and Vision Science at the
University of New South Wales.
A total of 154 participants were recruited
in the study, of which 77 exhibited clinically
detectable incomplete blinking and 77 did not.
Blink rate, dry eye symptomology, tear film
parameters and ocular surface characteristics
were assessed in a single clinical session. The
results demonstrated
that incomplete blinking
was associated with a
two-fold increased risk
of dry eye disease, as
defined by the global
consensus TFOS DEWS
II dry eye diagnostic
criteria. Participants exhibiting incomplete
blinking exhibited significantly higher levels
of symptoms and meibomian gland dropout,
as well as poorer tear film stability, lipid layer
thickness, expressed meibum quality, eyelid
notching and anterior blepharitis grades.
Interestingly, no significant correlations were
observed between blinking frequency and
ocular surface parameters.
The findings of the study provide evidence
in favour of the hypothesis that incomplete
blinking may predispose towards the
development of meibomian gland dysfunction
and evaporative dry eye, through diminishing
Fig 1. Partial meibomian gland drop out
the flow of meibomian lipids into the tear film,
which may potentially contribute towards
dropout and atrophy of the meibomian glands
(Fig 1). Furthermore, the potential association
between incomplete blinking and development
of meibomian gland dysfunction would also
support current recommendations of offering
blinking training as part of the multi-modal
management of dry eye disease.
References
1. Wang MT, Tien L, Han A, Lee JM, Kim D, Markoulli M, Craig JP. Impact
of blinking on ocular surface and tear film parameters. doi: 10.1016/j.
jtos.2018.06.001. Ocul Surf. 2018.
OSL: Ethnic differences in the paediatric ocular surface
By Ji Soo Kim, Dr Michael Wang and A/Prof Jennifer Craig
ASIAN ETHNICITY IS recognised to be a
significant risk factor for the development of dry
eye disease, with a higher prevalence and severity
of dry eye signs and symptoms consistently
reported in Asian populations relative to
Caucasian cohorts in the literature. However,
the effects of environmental differences
between Asian and Caucasian population
studies conducted in different parts of the
world, as well as the lack of consistency
in methodology of earlier studies, created
significant challenges when interpreting
their findings.
In a previous age and environmentallycontrolled
cross-sectional study 1 conducted
by the University of Auckland Ocular Surface
Laboratory (OSL), involving 74 co-located young
adults, aged between 18 to 30 years, the Asian
eye was found to exhibit a significantly higher
degree of meibomian gland dropout and
incomplete blinking, although no significant
ethnic difference in dry eye symptomology was
identified in this age group. It was hypothesised
that incomplete blinking may predispose towards
eventual meibomian gland atrophy (see story this
page) through reducing the flow of meibomian
secretions and potential blockage and
inflammation of the ductal system. In addition, it
was thought the ethnic differences in the ocular
surface observed may predispose towards a
greater severity of dry eye symptomology and
signs in the Asian eye with advancing age.
Asian ethnicity: a significant risk factor for dry eye
The TFOS DEWS II epidemiology report, released
in July last year, identified limited literature
on the natural history of dry eye disease, as
well as studies surrounding the status of the
ocular surface and tear film in the paediatric
population. To help address some of these gaps
in knowledge, an age and environmentallycontrolled
cross-sectional study 2 of 70 co-located
paediatric participants, aged between 5 and 18
years, was recently conducted by the OSL.
The results showed there were no significant
overall ethnic differences in tear film quality, dry
eye symptomology or meibomian gland dropout
between the Asian and Caucasian paediatric
cohorts. Nevertheless, in agreement with the
previous young adult study, a higher proportion
of Asian participants demonstrated incomplete
blinking than Caucasian participants. Ethnic
differences in meibomian gland morphology
patterns were also observed, with gland
shortening being more common in the Asian
paediatric eye, while gland tortuosity was
more frequently observed in the Caucasian
eye, although the reasons for this are as yet
unknown. Furthermore, Asian participants
without an eyelid crease were found to exhibit a
higher degree of inferior lid wiper epitheliopathy
and corneal astigmatism, which would both
appear to suggest possible effects from higher
levels of eyelid tension.
Overall, the findings of the study suggest that
eyelid anatomy and tensions may potentially
be implicated in the Asian ethnic predisposition
towards incomplete blinking and meibomian
gland dysfunction, which may eventually
manifest with increased prevalence and severity
of dry eye disease with advancing age.
References
1. Craig JP, Wang MT, Kim D, Lee JM. Exploring the Predisposition of the Asian
Eye to Development of Dry Eye. Ocul Surf. 2016 Jul;14(3):385-92.
2. Kim JS, Wang MT, Craig JP. Exploring the Asian ethnic predisposition to dry
eye disease in a paediatric population. Ocul Surf. 2018 (in press).
22 | NEW ZEALAND OPTICS SEPTEMBER 2018

LAUNCHING
LATE 2018

DRY EYE 2018
OSL: Fluorescein and tear
film stability assessment
By Dr Michael Wang, Dr Jennifer Mooi, Joevy Lim, Dr Andreas Müller and A/Prof Jennifer Craig
TEAR FILM STABILITY measurement is
an integral component of the assessment of
dry eye disease. Although ocular instillation
of sodium fluorescein via impregnated strips
is conventionally used to visualise tear film
breakup, it is also recognised to destabilise
the tear film, reducing stability measurements
obtained. In recent years, however, automated,
non-invasive measurement techniques have
become available and are recommended by
the global consensus TFOS DEWS II dry eye
diagnostic criteria, in preference to fluorescein
breakup time measurement.
Two recent studies conducted by the
University of Auckland Ocular Surface
Laboratory (OSL) compared tear film stability
measurements obtained by the traditional
fluorescein and contemporary non-invasive
methods.
The first, recently published randomised
crossover study 1 of 74 participants (including
37 dry eye patients and 37 age, gender and
ethnicity-matched healthy participants)
compared measurements obtained by the
conventional fluorescein method with those
from an automated non-invasive corneal
topographer (Oculus Keratograph 5M) and
evaluated their respective discriminative ability
in detecting symptomatic dry eye.
Automated non-invasive keratograph
breakup time (NIKBUT) measurements were
found to be significantly longer than fluorescein
breakup time in both dry eye patients and
healthy participants. The optimal diagnostic
cut-off for NIKBUT was also longer, at ≤9
seconds, than the best cut-off point for the
fluorescein breakup time, which was shown
to be ≤5 seconds. Furthermore, NIKBUT
measurements had better discriminative ability,
sensitivity and specificity than the conventional
fluorescein breakup time test.
The other prospective crossover study 2 of
41 participants compared tear film breakup
time measurements obtained non-invasively,
with minimal fluorescein instillation (1μL),
and conventional fluorescein strips (15-30
μL). The results showed that breakup time
values measured with conventional fluorescein
instillation were significantly shortened, while
those obtained with tiny amounts of fluorescein
instillation compared much better to noninvasive
measurement techniques.
The findings suggest, that where noninvasive
measures are not available, we can
reduce the destabilising impact of fluorescein on
clinical measurements of tear film stability by
minimising the volumes we instil!
References
1. Wang MT, Craig JP. Comparative Evaluation of Clinical Methods of Tear Film
Stability Assessment: A Randomized Crossover Trial. JAMA Ophthalmology.
2018;136(3):291-294.
2. Mooi JK, Wang MT, Lim J, Müller A, Craig JP. Minimising instilled volume
reduces the impact of fluorescein on clinical measurements of tear film
stability. Contact Lens Anterior Eye. 2017;40(3):170-174.
Automated non-invasive keratograph breakup time measurements
OSL: Lid cleanser versus baby shampoo for blepharitis
By Dr Justin Sung, Dr Michael Wang, Sang Lee, Dr Isabella Cheung, Salim Ismail, Prof Trevor Sherwin and A/Prof Jennifer Craig
BLEPHARITIS IS A common ophthalmic
condition characterised by chronic eyelid
inflammation and associated symptoms
of ocular irritation and dry eye. It can have
a profound impact on quality of life. The
management of blepharitis involves both
the prevention and treatment of intermittent
episodes of inflammatory exacerbation and
regular eyelid hygiene regimens. Warm compress
therapies are commonly advised for long-term
symptomatic relief.
The efficacy of a dedicated eyelid cleansing
formulation (TheraTears SteriLid) and diluted
baby shampoo in blepharitis patients was
compared in a recently published, doublemasked,
randomised trial conducted by
the University of Auckland Ocular Surface
Laboratory (OSL) 1 . A total of 43 participants
with clinical signs of blepharitis were recruited
and were randomised to apply the dedicated
eyelid cleanser to one eye and diluted baby
shampoo to the fellow eye (from bottles that
Blepharitis
were identical other than the marking of right
and left eye), twice daily for four weeks. Ocular
symptoms, tear film quality, ocular surface
characteristics and inflammatory markers were
assessed at baseline and following the treatment
period.
The results of the trial showed that blepharitis
was improved, clinically, by both treatments,
including SPEED symptomology scores, superior
lid wiper epitheliopathy, seborrhoeic lash
crusting and lash misdirection grading. However,
improvements in tear film lipid layer thickness,
inferior lid wiper epitheliopathy, cylindrical
collarette grading and MMP-9 expression (a
marker of ocular surface inflammation), as well
in SANDE symptom scores, occurred only with
the dedicated eyelid cleanser. Furthermore,
meibomian gland orifice capping and MUC5AC
expression (a marker of goblet cell function)
were found to actually worsen with baby
shampoo treatment.
Overall, the dedicated eyelid cleansing
formulation demonstrated superior efficacy and
was the preferred treatment among blepharitis
patients. The findings also highlighted potential
long-term adverse effects of baby shampoo
treatment on goblet cell function that warrant
further exploration in future studies.
References
1. Sung J, Wang MT, Lee SH, Cheung IM, Ismail S, Sherwin T, Craig JP.
Randomized double-masked trial of eyelid cleansing treatments for
blepharitis. Ocular Surface. 2018;16(1):77-83.
24 | NEW ZEALAND OPTICS SEPTEMBER 2018

OSL: Desktop humidifier for DED relief?
By Dr Michael Wang, Evon Chan, Linda Ea, Clifford Kam,
Yvonne Lu, Dr Stuti Misra and A/Prof Jennifer Craig
IN RECENT DECADES, the significant
increase in digital screen use, both at home and
at work, has been accompanied by a growing
prevalence of dry eye disease worldwide. The
high visual and cognitive load associated with
digital screen use, along with sustained visual
attention, can result in a reduction of blinking
frequency by a factor of two or three times.
Reduced blinking frequency or quality can
compromise the delivery and distribution of
tear film components over the ocular surface,
leading to tear film destabilisation and breakup,
and the consequent development of dry eye
symptoms.
Furthermore, low humidity environments
are common in the modern workplace with the
widespread use of air conditioning and central
heating. These are recognised to exacerbate
dry eye severity through creating a larger water
vapour pressure gradient between the ocular
surface and external environment, increasing
the rate of aqueous tear evaporation.
The efficacy of a USB-powered desktop
humidifier to provide dry eye relief was
examined in a recently published, masked,
randomised, crossover trial conducted by
the University of Auckland Ocular Surface
Laboratory (OSL) 1 . A total of 44 participants
were recruited and randomised, on separate
days, to a one-hour period of continuous
computer use, with and without exposure to the
desktop humidifier. Tear film parameters and
ocular comfort were assessed before and after
computer use.
The results of the study showed that while
the desktop humidifier effected only a modest
increase in relatively humidity locally, a
significant increase in tear film stability was
observed, which was associated with a higher
proportion of participants reporting greater
subjective ocular comfort.
References
1. Wang MT, Chan E, Ea L, Kam C, Lu Y, Misra SL, Craig JP. Randomized Trial
of a Desktop Humidifier for Dry Eye Relief in Computer Users. Optometry &
Vision Science. 2017;94(11):1052-1057.
14th Annual
Scientific Conference
1/2 day workshops
Saturday afternoon
3rd November 2018
Optometry Conference
Sunday 8.00am - 5.00pm
November 4th 2018
Join us for another exciting weekend in
support of Optometrists, Dispensers and Staff
Venue: Waipuna Hotel & Conference Centre.
58 Waipuna Rd, Mt Wellington Auckland
Book now: for your 2018/2019 CPD Credits
(including Therapeutics)
Register online: https://www.eyeinstitute.co.nz/healthprofessionals/events
Email: professionaleducation@eyeinstitute.co.nz
We are honoured to present our 2018 international
guest speaker, Professor Joanne Wood.
Joanne is
a Professor in the School of Optometry and Vision
Science and has extensive research experience in
several areas: vision and driving, vision and falls and
clinical psychophysics. Her research experience spans
over 25 years and includes a PhD in Visual Science
at Aston University UK, followed by a Post-Doctoral
Fellowship in Clinical Psychophysics. In 1991, Professor
Wood established a vision and driving research
laboratory. This lab uses an experimental design, incorporating measurements of actual
driving performance on a closed circuit driving course, as well as on the open road,
rather than making indirect judgements via crash rate data or driving simulators. This
unique approach to investigating vision, ageing and driving has attracted a number
of international scholars to collaborate in research projects led by Professor Wood.
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WWW.EYEONOPTICS.CO.NZ | 25

DRY EYE 2018
OSL:Tear supplements vs the environment
By Dr Akilesh Gokul, Dr Michael Wang and A/Prof Jennifer Craig
ADVERSE ENVIRONMENTAL
CONDITIONS, including high airflow velocity
and low relative humidity, are recognised to
exacerbate dry eye signs and symptoms. Topical
artificial tear supplements are among the most
commonly used therapies for dry eye disease,
although the protective effects of eye drop
application prior to the exposure of adverse
environmental conditions have not yet been
established.
The prophylactic efficacy of a lipomimetic
eye drop (Systane Balance) and a non-lipid
containing drop (Systane Ultra) were compared
in a recently published, double-masked,
randomised trial conducted by the University
of Auckland Ocular Surface Laboratory (OSL)¹.
A total of 30 patients with symptomatic dry eye
were recruited and randomised to lipomimetic
drop application in one eye and the non-lipid
containing drop in the fellow eye. Participants
were then exposed to a validated simulated
adverse environment model and tear film
quality and dry eye symptomology assessed
at baseline and following exposure to the
simulated adverse environment.
The results of the trial showed that
both therapies resulted in an immediate
improvement in tear film stability and
prevented its decline below baseline following
simulated adverse environment exposure.
However, improvements in tear film lipid layer
quality and the prevention of its decline below
baseline was limited only to the lipomimetic
drop which, interestingly, also demonstrated
superior post-instillation and post-exposure
tear film stability, lipid layer thickness and
ocular comfort than the non-lipid containing
eye drop.
Overall, the findings demonstrated
that application of both lipid and nonlipid
containing eye drops conferred
prophylactic efficacy against exposure
to adverse environmental conditions in
patients with symptomatic dry eye. However,
the lipomimetic drop conferred superior
protective effects and was the preferred
treatment among dry eye patients.
References
1. Gokul A, Wang MTM, Craig JP. Tear lipid supplement prophylaxis
against dry eye in adverse environments. Cont Lens Anterior Eye. 2018
Feb;41(1):97-100.
Blink test for DED
By Prof James Wolffsohn, Maria Vidal-Roht,
Sonia Trave Huarte, A/Prof Jennifer Craig, Lexia Ah-Kit
and Dr Michael Wang
THE OPTREX DRY EYE BLINK TEST 1 is a simple,
online self-assessment tool which provides
patients and clinicians with a convenient and
rapid preliminary screening instrument for dry
eye disease, without the need for specialist
instrumentation or the instillation of ocular
dyes. The Blink Test measures the amount of
time taken following two, non-forceful blinks
for a patient to experience symptoms of ocular
discomfort or dry eye.
A recently published diagnostic accuracy study,
jointly conducted by the Aston University
Ophthalmic Research Group and the University
of Auckland Ocular Surface Laboratory,
evaluated the discriminative ability of the Blink
Test in detecting patients with dry eye disease,
as defined by the global consensus TFOS DEWS II
diagnostic criteria.
A total of 87 participants were recruited and
the study results demonstrated that the Blink
Test values were significantly correlated with
tear film stability, dry eye symptomology
scores, conjunctival staining and lid wiper
epitheliopathy. At the optimal diagnostic cut
off of

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28 | NEW ZEALAND OPTICS SEPTEMBER 2018

DRY EYE 2018
OSL: Cosmetics and the tear film
By Dr Michael Wang and A/Prof Jennifer Craig
Eye cosmetics are widely used by mostly female populations of all age
groups globally for religious, cultural and cosmetic purposes. The literature
surrounding the effects of eye cosmetics on tear film quality and dry
eye disease was assessed by a recent review 1 conducted by University of
Auckland Ocular Surface Laboratory (OSL) researchers.
Consistent evidence, both cross-sectional and prospective, was identified
for the migration of cosmetic products across the eyelid margin and into
the tear film. This compromises the quality of the surface lipid layer of
the tear film and predisposes towards tear film instability and dry eye
symptoms. Multiple adverse effects and complications associated with
eye cosmetic wear have also been reported, raising the possibility that
tear film contamination with cosmetic products may be associated with
ocular surface inflammatory responses, which can contribute to further
predisposition towards the development of dry eye disease. Prospective
studies have also shown that eyeliner application at the inner eyelash line,
known as ‘tightlining’, results in a higher degree of tear film contamination
and ocular discomfort than application to the outer periocular skin.
Finally, a recently published investigator-masked randomised trial of 50
participants 2 , conducted by OSL, also demonstrated that eye cosmetic wear
may have the potential to compromise the efficacy of topical lipid-based
dry eye treatments.
References
1. Wang MT, Craig JP. Investigating the effect of eye cosmetics on the tear film: current insights. Clinical Optometry.
2018;10:33-40.
2. Wang MT, Cho ISH, Jung SH, Craig JP. Effect of lipid-based dry eye supplements on the tear film in wearers of eye
cosmetics. Contact Lens Anterior Eye. 2017;40(4):236-241.
Microblepharon exfoliation to improve CL comfort
By Sowjanya Siddireddy, Dr Ajay Kumar Vijay, Dr Jackie Tan-Showyin and Prof Mark Willcox
CONTACT LENS WEAR is associated with discomfort. This presents a
real problem for wearers, practitioners and industry as discomfort is one
of the main reasons for contact lens wearers to drop out of lens wear.
At the School of Optometry and Vision Science at the University of
New South Wales we have recently studied whether changes to ocular
microbiota are associated with discomfort during wear and whether
microblepharon exfoliation of the lid margin changes the ocular
microbiota and if this is associated with improved comfort.
We enrolled 30 contact lens wearers, measured their comfort during
lens wear using the CLDEQ-8 questionnaire and swabbed their eyelids.
The swabs were then cultured to identify and enumerate the types of
microbes colonising the lids. Culture and identification used standard
microbiological techniques. We then either washed their eyelids once with
a foam cleanser or used the foam cleanser along with microblepharon
exfoliation with BlephEx. After treatment, we gave them the CLDEQ-8
questionnaire again and swabbed their eyelids for microbial identification
and enumeration. We then left the subjects for 7-10 days and repeated the
CLDEQ-8 and microbial workup to assess which changes lasted for that
time period.
Treating eyes with either a foam cleanser or the foam cleanser with
microblepharon exfoliation improved the comfort of symptomatic lens
wearers (CLDEQ-8 >12 points). By 7-10 days after treatment, with the
foam cleanser alone, the scores of symptomatic wearers improved by two
points on the CLDEQ-8 scale, but they remained above the cut-off of 12
and so were still classified as symptomatic. On the other hand, use of the
foam cleanser with the microblepharon exfoliation improved the CLDEQ-8
scores by six points and most symptomatic wearers had scores below 12,
converting them to asymptomatic wearers.
Symptomatic lens wearers were found to have approximately 50% more
microbes on their lids than asymptomatic wearers. The foam cleanser
alone reduced the number of microbes on eyelids of symptomatic wearers
by approximately 50% within 7-10 days after treatment. Treatment with
microblepharon exfoliation reduced microbe numbers by 60% in the
same post-treatment timeframe. Gram-negative bacteria were isolated
from symptomatic lens wearers only and were significantly reduced from
baseline to follow-up with both treatments.
This data points to the importance of contact lens wearers maintaining
good lid hygiene. Practitioners should consider treating the lids of contact
lens wearers who are complaining of discomfort during wear and also
talking to the wearers about how they could improve the hygiene of their
lids.
Sowjanya Siddireddy is a clinician and researcher at the School of Optometry and Vision
Science at the University of New South Wales in Sydney, working with research fellows Dr
Ajay Kumar Vijay and Dr Jackie Tan-Showyin, and with Professor Mark Willcox. Prof Wilcox
specialises in ocular microbiology, ocular inflammation and infection and bio-prospecting.
His current research focuses on understanding the aetiology of adverse events and
comfort during contact lens wear, including adhesion and biofilm formation of ocular
pathogenic microbes and development of novel antimicrobial surfaces.
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WWW.EYEONOPTICS.CO.NZ | 29

DRY EYE 2018
Cataract surgery and dry eye
By Dr Stuart Carroll
CATARACT SURGERY IS one of the most
common elective surgical procedures performed
worldwide. Advancements with surgical
instrumentation and lens implant technology
have made it increasingly popular as a treatment
for both visual rehabilitation and refractive
correction. Patient expectations have never been
higher, and superb results with rapid recovery
are readily achievable. Sounds great, right, so
what’s the problem? “My eyes are constantly
irritated… they were never like that before the
surgery, doctor!”
Unfortunately, dry eye disease (DED), while
frequently dismissed as a minor annoyance
following cataract surgery, can be a significant
cause of patient dissatisfaction, visual symptoms
and poor surgical outcomes. Preoperatively,
accurate biometric measurements require an
optimal ocular surface state 1 . Furthermore, the
numerous presbyopia-correcting IOL options that
are becoming increasingly popular, are notoriously
unforgiving with regard to visual quality in the
presence of a suboptimal ocular surface.
The prevalence of ocular surface signs in the
patient demographic that undergoes cataract
surgery is extremely high. In the PHACO
study, 77% of patients had corneal staining
preoperatively 2 . Although, many of these
patients may be asymptomatic 3 , disruption of
the delicate homeostasis of the tear film and
ocular surface can lead to manifestation of
symptoms which then become frustratingly
difficult to manage reliably, despite the
significant advances in our understanding of
DED and its treatment options. Several studies
have indicated that patient symptoms and signs
are negatively influenced by cataract surgery
and some may take up to six months to recover 4 .
The TFOS DEWS II report represents an
extensive body of work led by world experts in
dry eye, and their recently published iatrogenic
dry eye report presents a comprehensive
literature review which includes cataract
surgery 5 . There is no question that many
interventions involved in cataract surgery are
responsible for post-operative DED. The most
likely perpetrators are topical medications
(and their preservatives) used pre- and postoperatively,
oxygen free radicals and proinflammatory
cytokines generated in response
to surgical trauma, and the corneal incisions
which invariably sever corneal nerves. Similar,
though more extensive, corneal nerve injury is
well described following LASIK surgery where
postoperative dry eye is one of the chief sources
of postoperative dissatisfaction. Light toxicity
from the operating microscope has also been
implicated. Diabetic patients in particular seem
to be more at risk of iatrogenic DED 5 .
Therefore, a comprehensive dry eye
evaluation should be performed for all
prospective cataract surgery patients. Preoperative
recognition and optimisation of DED
signs and symptoms is a critically important
factor in managing such patients. Ideally this
should begin at the point of referral, when
surgery is being considered. The TFOS DEWS
II reports are an ideal source for up-to-date
diagnosis and management recommendations.
Avoiding topical preservatives in at-risk
patients, minimising postoperative drop toxicity
and actively managing dry eye symptoms with
Fig 1. Fluorescein dye showing poor tear film homogeneity and
break-up. Credit: Dr Dean Corbett
topical lubricants where necessary are simple
measures that can help post-operatively.
On the horizon, “dropless cataract surgery”
(where intraocular slow-release preparations of
steroid and antibiotic are used instead of topical
post-operative medications) may be a useful
step forward in preventing DED in cataract
surgery patients. Stay tuned!
Laser refractive surgeons recognised all of
this long ago and consider it standard care to
treat dry eye pre- and post-operatively. We
should all adopt the same standard of care for
our cataract patients.
References
1. Epitropolous AT et al. Effect of tear osmolarity on repeatability of keratometry
for cataract surgery planning. J Cat Refract Surg 41(8):1672-7.
2. Trattler WB et al. The Prospective Health Assessment of Cataract Patients’
Ocular Surface (PHACO) study: the effect of dry eye. Clin Ophthalmol. 2017;
7(11):1423-30.
3. Cochener B et al. Prevalence of meibomian gland dysfunction at the time
of cataract surgery. J Cataract Refract Surg. 2018 Feb;44(2):144-148
4. Xue W et al. Long-term impact of dry eye symptoms on vision-related quality
of life after phacoemulsification surgery. Int Ophthalmol. 2018 Feb 1. doi:
10.1007/s10792-018-0828-z. [Epub ahead of print]
5. Gomes JAP et al. TFOS DEWS II iatrogenic report. The Ocular Surface
(2017) 15(3):511-38.
Dr Stuart Carroll is a consultant ophthalmologist
at Auckland Eye and Greenlane Clinical Centre in
New Zealand with specialist knowledge in cataract
and refractive surgery, strabismus and paediatric
ophthalmology.
Castor oil for dry eye? Demodex?
By Dr Emma Sandford and Grant Watters, with A/Prof Jennifer Craig
CASTOR OIL HAS a long and ancient history
as a traditional remedy for skin, scalp and hair
ailments, and internally for gastrointestinal
and reproductive applications. It is even
mentioned in herbal medicine lists on papyrus
from ancient Egypt.
Today, castor oil continues to appear
intermittently in online searches for natural
treatments for blepharitis, so we’ve decided
to study its effects in relation to dry eye,
specifically with respect to anterior blepharitis
and Demodex mites, and examine its likely
mechanisms of action, in a scientific manner.
Castor oil’s main constituent is ricinoleic acid,
which has a number of properties applicable
to the different facets of the pathophysiology
of blepharitis and dry eye. It is an emollient,
anti-inflammatory, anti-microbial, anti-oxidant,
and a surfactant with lipid layer-forming
abilities, so it spreads across the tear film in
a thin layer. It penetrates the lash follicles
and there is every reason to
suspect it might interfere with
the physiology of Demodex mites,
rather like tea tree oil.
We are employing a unique
rollerball application method,
which ensures application of a thin
film close to the lid margins. The
hypothesis is this may have some
therapeutic benefit in controlling blepharitis and
Demodex, along with the possibility that a small
degree of ingress into the tear film will enhance
the lipid layer and could potentially address lipid
layer deficiency which leads to dry eye symptoms
associated with blepharitis.
Under the guidance of Associate Professor
Jennifer Craig, we are conducting a prospective,
randomised, investigator-masked trial of
topically-applied castor oil for blepharitis as
an optometry honours research project. This
is being conducted by Part V students, Marna
Auckland optometry student
Marna Claassen demonstrating the
castor oil rollerball lid applicator
Claassen, Lauren Curd and Alice
Jackson, who are recording
a range of subjective and
objective parameters to elicit
symptomatic and biometric
changes of the eyelids and
tear film, including changes in
ocular surface inflammatory
biomarkers. We are excited to
find out, when the data are
unmasked at the conclusion
of the study, whether a onemonth
application period has
resulted in improvements in these parameters
and lower titres of inflammatory markers.
If so, this could infer long-term benefits
with respect to minimising ocular surface
inflammation and reducing the incidence of
dry eye in blepharitis patients.
We are currently recruiting for this study. For
more information and to check eligibility
please call or text us on 022 EYE PAIN.
Dr Emma Sandford is a GP in the Bay of Plenty and
an honorary academic, and Grant Watters is an
optometrist and researcher at the University of
Auckland.
30 | NEW ZEALAND OPTICS SEPTEMBER 2018

Understanding the “lid wiper”
By Dr Alex Muntz
WE BLINK AROUND 10,000 times a day, with the eyelids traversing the
length of a football pitch in distance each day. Wiping over the eye’s
surface with every blink is the “lid wiper”, a 1-2mm thin portion of the
inner eyelid margin. We assume that friction is increased here during
blinking, especially when lubrication is sub-par because of an altered
tear film, or by wearing contact lenses. Higher friction may induce a
mechanical or hyperosmotic insult
of the lid wiper, driving symptoms
of dryness and discomfort in dry eye
and contact lens patients.
Fig 1. LWE on the everted upper eyelid
margin, shown by lissamine green staining
Clinically, this association appears
to be reflected in “lid wiper
epitheliopathy” (LWE), a staining
pattern observed at the upper
and/or lower lid margins following
lissamine green instillation and lid
eversion (Fig 1). But if vital stains
are able to highlight a degree of cellular damage, what does this damage
look like at a cellular level?
While dry eye and contact lens wear are recognised to be associated
with cellular changes of the ocular surface (including within the cornea,
limbus and bulbar conjunctiva), we know surprisingly little about
clinically-relevant variations in the cellular anatomy and physiology
of the lid wiper; the area in exclusive apposition with the eye’s surface
during blinking. The cornea, bulbar or tarsal conjunctival are commonly
and easily assessed by application and removal of a membrane to
which superficial cells adhere. This “impression cytology” technique is
a quick and convenient tool for sample collection from patient prior
to histological cellular analysis. However, the narrow, sharply curved
lid margin does not easily lend itself to such a sampling method. The
optimisation of impression cytology for lid marginal use was the focus of
my PhD studies at the University of Waterloo in Canada. During this time,
we determined the ideal membrane material, the optimal location, angle
and pressure, and the duration of application (Fig 2). We chose specialised
histological dyes that change their colour according to the keratinisation
level of cells to reflect friction at the lid margin (Fig 3).
Armed with this new tool, lid marginal epithelial cells were collected from
patients presenting with varying levels of LWE, including contact lens
wearers and non-lens wearers with a range of self-reported discomfort
and dryness levels. By investigating the cellular morphology (size, shape,
state, type, number of cells etc.) of the lid margin and its correlation with
clinical signs and subjective symptoms, we are hoping to shed new light
on the role of this region for dry eye and contact lens patients.
A video demonstrating this technique as well as our published methods
paper are available at www.imuntz.com/ic. Stay tuned for a full report on
these studies in an upcoming issue of
NZ Optics!
Reference and pictures reproduced with permission, courtesy
of A Muntz, K van Doorn, L N Subbaraman, L W Jones,
Impression cytology of the lid wiper area, J Vis Exp. (2016)
e54261–e54261.
Dr Alex Muntz, an optometrist, is a postdoctoral
research fellow in the Ocular Surface
Laboratory at the University of Auckland and
was previously a clinical research scientist
with the University of Waterloo’s Centre for
Ocular Research & Education
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Fig 2. Impression cytology on
the upper lid wiper region
Fig 3. Cells of the lid wiper region
show varying morphology and
different keratinisation degrees
through differential staining dyes: no
keratinisation (a); advanced keratinisation
(c); and incipient keratinisation (b)
WWW.EYEONOPTICS.CO.NZ | 31

DRY EYE 2018
Ocular allergy
and dry eye
By Prof James Wolffsohn
OCULAR ALLERGY REPRESENTS a group of
hypersensitivity disorders that primarily affects
the conjunctiva.
The most common form of ocular allergy
is seasonal allergic conjunctivitis (SAC),
accounting for 90% of cases¹ , ². The most
prevalent allergens in SAC are grass, tree and
weed pollen, and outdoor moulds². In the
United Kingdom, the prevalence of ocular
allergy to grass pollen in patients attending
optometric practice is estimated to be 8%³ – no
data is currently available from Australasian
countries.
Similar to dry eye, although the signs and
symptoms of SAC are usually mild, they may
hinder school performance, work productivity
and everyday tasks such as driving 4 . The
primary treatment strategy for SAC involves
avoidance of the offending allergen to prevent
the initiation of the allergic response. However,
complete avoidance is not often possible and
use of topical anti-allergic medications is
required when signs and symptoms occur 5 .
While non-pharmacological treatments, such
as artificial tears developed for dry eye and cold
compresses have been used for many years, in
conjunction with allergen avoidance strategies
and anti-allergic medications to help bring
about symptomatic relief 5,6 , evidence showing
the effectiveness of this approach has only
relatively recently been published 7 . In this study,
patients had controlled exposure to grass pollen
and either used cold compresses or artificial
tears, resulting in therapeutic effects on the
signs and symptoms of allergic conjunctivitis. A
cold compress enhanced the use of epinastine (a
mast cell stabiliser/antihistamine combination)
and was the only treatment to reduce symptoms
to baseline within an hour of antigenic
challenge. Signs of allergic conjunctivitis were
generally reduced most by a combination of
cold compress and artificial tears or epinastine.
In a separate, recent study, acute allergic
rhinoconjuctivitis has been shown to be
characterised by tear hyperosmolarity, which
can be rehabilitated with the administration of
hypotonic artificial tears, much like dry eye 8 .
Considerable overlap of reported symptoms
of itch and dryness has been reported in groups
with presumed dry eye and seasonal allergic
conjunctivitis 9 . As with ocular allergy, there can
be seasonal (summer and winter) and weatherrelated
aspects to dry eye symptoms 10 . Similar
biomarkers for the biological ‘diagnosis’ of both
dry eye and ocular allergy have been proposed 11 ,
along with imaging techniques such as in-vivo
confocal microscopy 12 , but these have not been
adopted clinically.
Dry eye symptoms are generally greater in
those with ocular allergy 13 and some ocular
allergy medications can induce signs and
symptoms of dry eye 14 . Hence it would seem
that clinically the conditions are often confused
and careful questioning of when the symptoms
occur is advised to aid with the selection of
appropriate management.
References
1. Abelson MB, Leonardi A, Smith L. The mechanisms, diagnosis and treatment
of allergy. Rev Ophthalmol 2002;9:74-84.
2. Bielory L. Ocular allergy overview. Immunology Allergy Clin 2008;28:1-23.
3. Wolffsohn JS, Naroo SA, Gupta N, Emberlin J. Prevalence and impact of
ocular allergy in the population attending UK optometric practice. Contact
Lens Ant Eye 2011;34:133-8.
4. Smith AF, Pitt AD, Rodruiguez AE, et al. The economic and quality of life
impact of seasonal allergic conjunctivitis in Spanish setting. Ophthalmic
Epidemiol 2005;12:233-42.
5. Bielory L. Ocular allergy treatment. Immunology Allergy Clin 2008;28:189-
224.
6. Chigbu DI. The management of allergic eye disease in primary care. Contact
Lens Ant Eye 2009;32:260-72.
7. Bilkhu PS, Wolffsohn JS, Naroo SA, Robertson L, Kennedy R. Effewctivenes
of non-pharmaceutical treatments for acute seasonal conjunctivitis.
Ophthalmology 2014;121:72-8.
8. Nitoda E, Lavaris A, Laios K, Androudi S, Kalogeropoulos CD, Tsatsos M,
Damaskos C, Garmpis N, Moschos MM. Tear Film Osmolarity in Subjects
with Acute Allergic Rhinoconjunctivitis . In Vivo 2018;32:403-8.
9. Hom MM, Nguyen AL, Bielory L. Allergic conjunctivitis and dry eye
syndrome. Annals Allergy, Asthma, Immunol 2012;108:163-6.
10. van Setten G, Labetoulle M, Baudouin C, Rolando M. Evidence of seasonality
and effects of psychrometry in dry eye disease. Acta Ophthalmol 2016;94:499-
506.
11. Enriquez-de-Salamanca A, Bonini S, Calonge M. Molecular and cellular
biomarkers in dry eye disease and ocular allergy. Curr Opin Allergy Clin
Immunol 2012;12:523-33.
12. Villani E, Mantelli F, Nucci P. In-vivo confocal microscopy of the ocular
surface: ocular allergy and dry eye . Curr Opin Allergy Clin Immunol
2013;13:569-76.
13. Vehof J Smitt-Kamminga NS, Nibourg SA, Hammond CJ. Predictors of
discordance between symptoms and signs in dry eye disease. Ophthalmol
2017;124:280-6
14. Ousler GW, Workman DA, Torkildsen GL. An open-label, investigatormasked,
crossover study of the ocular drying effects of two antihistamines,
topical epinastine and systemic loratadine, in adult volunteers with seasonal
allergic conjunctivitis. Clin Therapeutics 2007;29:611-6.
Professor James Wolffsohn is pro-vice chancellor of
Aston University, Birmingham, England and was a subcommittee
chair for TFOS DEWS II. His main research
areas include the development and evaluation of
ophthalmic instrumentation, contact lenses, intraocular
lenses and the tear film.
32 | NEW ZEALAND OPTICS SEPTEMBER 2018

DED and the
Dunedin Study
By Dr Graham Wilson, A/Prof Jennifer Craig and Dr
Michael Wang
THE DUNEDIN MULTIDISCIPLINARY
Health and Development Study is a wellestablished,
large longitudinal study on human
health, development, ageing and behaviour,
which has been ongoing for more than 40 years.
The study has been tracking more than 1000
participants since they were born in 1972 or
1973. In 2017, for the first time, dry eye disease
(DED) was included as part of the study, as the
participants turn 45.
TFOS DEWS II identified significant gaps in
the existing dry eye literature, including a lack
of population-based prevalence studies from the
Southern Hemisphere over the past decade, as
well as limited scientific literature investigating
the natural history of DED. The TFOS DEWS
II epidemiology subcommittee also identified
a significant shortage of scientific evidence,
which is needed to provide a comprehensive
understanding of the risk factors for DED and
to better understand the relationship between
medical conditions and dry disease.
It is hoped that the dry eye arm of the
Dunedin Study will be able to help address
some of the identified gaps in the current dry
eye literature, through characterising ocular
surface and tear film parameters within a
large, age-controlled cohort based in the
Southern Hemisphere, exploring the potential
interactions between systemic conditions and
DED and assessing whether dry eye may be a
biomarker of the ageing process.
Data collection is currently well underway
and it is hoped the findings will be released over
the next two years.
Dr Graham Wilson is a Gisborne-based ophthalmologist
and principal investigator for all eye-related matters on
the Dunedin Study. A/Prof Jennifer Craig and Dr Michael
Wang are based at the Ocular Surface Laboratory at the
University of Auckland.
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33

DRY EYE 2018
Dry eye and autologous serum
By Dr Nick Mantell
THE TEAR FILM and ocular
surface are extremely complex,
with tear film playing a vital role
in maintaining ocular surface
health. Not only does it provide
lubrication but also many
neuropeptides, vitamins and
growth factors essential for the
health of the corneal epithelium.
Given the complexity of the tear
film, it seems a small miracle that it
functions normally in anyone.
Meanwhile dry eye disease
(DED) is encountered on a daily
basis by eye health professionals
and accounts for a range of mild
to severe discomfort symptoms
(pain, burning sensations, eye
fatigue, light sensitivity, redness
etc.) made worse by virtually
all types of ocular surgery. The
worsening of this condition
post-surgery is fortunately
present for only a finite period for
most people and will eventually
return to its preoperative level.
As ophthalmologists, we see this
regularly after refractive laser
procedures, but also after cataract
and retinal surgery (see p30). Less
commonly, surgery exacerbates
severe ocular surface disease
following chemical trauma, or
associated with neurotrophic
epithelial defects, or conjunctival
cicatrising conditions like Stevens
Johnston syndrome.
“...SEDs are recognised by most
factors in the tear film are vital to
the health of the ocular surface,
supplementing these proteins
has not, to date, been an integral
component of DED treatment.
This has, in part, been because
the actions of these factors have
not been well understood, but it
has also been difficult to isolate
ophthalmologists as an important option
for some dry eye disease patients who have
not responded to other treatments.”
Traditionally when treating
DED, we focus on optimising the
lipid layer on the surface of the
tear film to reduce the evaporation
of tears and facilitate spreading of
the tear film on the ocular surface;
maintaining or supplementing the
aqueous layer to normalise the
osmolarity of the tear film; and
treating any concurrent ocular
inflammation, typically with
steroids.
Although it is recognised that
the neuropeptides and growth
and produce these proteins. With
the increasing recognition of
the prevalence and significant
socioeconomic costs of this
condition, however, there has been
renewed interest in DED.
In the 1970s, doctors recognised
that many of the proteins and
growth factors present in the tear
film were also present in serum.
Autologous serum eye drops
have been used with considerable
success in patients with severe
chemical burns. Then, in the 1980s,
the application of serum eye drops
was extended to the treatment
of other forms of severe ocular
surface disease and non-healing
neurotrophic corneal ulcers,
resulting in significant clinical
evidence for the benefit of serum
in these conditions (Fig 1 and Fig
2).
In 1984, Fox et al published a
paper showing autologous serum
eye drops (SEDs) were helpful in
treating severe DED, leading to
increasing interest in this area.
However, it is still not considered
a mainstream therapy for this
condition. This is partly because
of the logistics of generating SEDs,
but also because clinical trials have
demonstrated variable benefits
with respect to treating dry eye.
A recent Cochrane review,
based on a limited number
of randomised clinical trials,
demonstrated that SEDs alleviate
dry eye symptoms better than
artificial eye drops for the first
couple of weeks, but data still
remains inconclusive regarding
clinical efficacy over long-term
periods.
SEDs are essentially prepared by
taking a patient’s blood, allowing
it to clot, then spinning it in a
centrifuge to separate the red
blood cells from serum. The serum
is then removed and mixed in
varying proportions with normal
saline, before being separated into
bottles, each with enough serum to
provide up to a week’s treatment.
These are then frozen and, at the
beginning each week’s treatment, a
single bottle is defrosted.
Preparing SEDs involves a
considerable amount of resource
and there is a small risk of
contamination if not handled
appropriately, so it’s important the
patient is fully informed about the
need for careful handling. There
are also strict protocols regarding
drop preparation. These may
vary from one service to another,
although my understanding is
that this is standardised across
the New Zealand blood service,
where the drops are 25% serum
and 75% saline. In other countries
50% or 100% serum mixtures
may be used. Unfortunately, there
isn’t consensus in the literature
regarding the most effective serum
concentration.
If a patient is unable to give
blood due to concurrent medical
conditions, it is also possible to
prescribe allogenic serum eye
drops. These are prepared in the
same way as autologous serum eye
drops, except the blood is sourced
from another patient.
As medical professionals, we
like our practices to be guided
by sound scientific evidence
regarding clinical efficacy. The
clinical evidence for treating
chemical ocular burns, severe
ocular surface disease (Stevens
Johnston Syndrome) and nonhealing
neurotrophic ulcers
is relatively strong, however a
similar level of evidence does not
yet exist for DED. Despite this,
SEDs are recognised by most
ophthalmologists as an important
option for some DED patients
who have not responded to other
treatments. It is generally accepted
that not all, but many patients
show clinical improvement on this
treatment, when other traditional
treatments fail.
The lack of evidence highlights
the difficulties in running clinical
trials on conditions that have, until
34 | NEW ZEALAND OPTICS SEPTEMBER 2018

ecently with TFOS DEWS II, been
relatively ill-defined, and where
clinical signs often show very
little relationship to the patient’s
symptoms.
Serum drops remain an evolving
therapeutic option. Some groups
are now using other blood-derived
products which may offer superior
therapeutic benefits over standard
SEDs. The first is Eye PRP which
uses a process to create platelet
enriched plasma with a reportedly
higher concentration of growth
factors. The second is ‘plasma rich
in growth factors’ PRGF which uses
a different process again to increase
the concentration of growth
factors. Preliminary trials involving
both preparations have shown
clinical benefits.
Finally, Moorfield’s Eye Hospital
ran a small trial where patients
were taught how to use a drop
of whole blood from a pinprick
on their finger, four times a
day for eight weeks. Significant
improvements were noted in
several parameters, such as visual
acuity, corneal staining, tear
break-up time (TBUT) and ocular
comfort index (OCI), but not the
Schirmer’ test.
So, we can expect more exciting
developments to come in this area.
References
1. Alio JL, Arnalich-Montiel F, Rodriguez AE. The role of
“eye platelet rich plasma (E-PRP)” for wound healing in
ophthalmology. Curr Pharm Biotechnol (2012)
2. Anitua E, de la Fuente M, Riestra A, Merayo-Lloves J,
Muruzabal F, Orive G. Preservation of biological activity
of plasma and platelet-derived eye drops after their
different time and temperature conditions of storage.
Cornea (2015)
3. Del Castillo JM, de la Casa JM, Sardina RC, et al.
Treatment of recurrent corneal erosions using autologous
serum. Cornea 2002;21:781–3.
4. Fox RI, Chan R, Michelson JB, et al. Beneficial effect
of artificial tears made with autologous serum in
patients with keratoconjunctivitis sicca. Arthritis Rheum
1984;27:459–61
5. Lopez-Plandolit S, Morales MC, Freire V, Grau AE,
Duran JA. Efficacy of plasma rich in growth factors for
the treatment of dry eye. Cornea (2011)
6. Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK.
Autologous serum eye drops for dry eye. Cochrane
Database Syst Rev (2017)
7. Than J, Balal S, Wawrzynski J, Nesaratnam N, Saleh
GM, Moore J, Sharma A et al. Fingerprick autologous
blood: a novel treatment for dry eye syndrome. Eye
(Lond) (2017)
8. Tsubota K , Goto E, Fujita H, et al. Treatment of dry eye
by autologous serum application in Sjögren’s syndrome.
Br J Ophthalmol 1999;83:390–5
9. Tsubota K , Satake Y, Ohyama M, et al. Surgical
reconstruction of the ocular surface in advanced ocular
cicatricial pemphigoid and Stevens-Johnson syndrome
[see comments]. Am J Ophthalmol 1996;122:38–52.
Dr Nick Mantell specialises in cataract,
laser vision correction and vitreoretinal
surgery with the Eye Institute in Auckland
and is a former clinical senior lecturer
with the Department of Ophthalmology
at Auckland University
Fig 1. Neurotrophic ocular surface disease, due to presumed HSV,
prior to treatment with SEDs
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tear film break-up time. Lacritec is specially formulated based from this research and because it is
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WWW.EYEONOPTICS.CO.NZ | 35

DRY EYE 2018
Diabetes, dry eye and ‘substance P’?
By Drs James Slater and Stuti Misra
DIABETES HAS NOW reached epidemic
proportions affecting millions of people across
the world. It is estimated around 54% of patients
with diabetes suffer from some degree of dry eye
syndrome 1 .
Patients with diabetes commonly complain of
burning and foreign body sensation in their
eyes. In severe cases, this may result in reduced
corneal sensitivity, aberrant wound healing
ability of the cornea, increased risk of infection
and the eventual development of diabetic
neurotrophic keratopathy 2 . Interestingly, there
is growing evidence of the involvement of
neurotransmitters in the tear film offering an
interesting potential pathway for future ocular
surface treatment strategies 3 .
Chronic hyperglycaemia, diabetic peripheral
neuropathy, decreased insulin levels,
microvasculopathy and systemic hyperosmotic
disturbances are the most common risk
factors for diabetes mellitus associated dry
eye syndrome (DMDES). Insulin is critical for
proliferation of the acinar lacrimal gland and
corneal epithelial cells, whereas hyperglycaemia
induces significant histological changes in the
lacrimal gland. This suggests a strong role of
oxidative stress in dry eye syndrome. A number
of factors, however, are responsible for ocular
surface changes in patients with diabetes which
ultimately may lead to corneal nerve damage
(fig 1).
Substance P is a neuropeptide released from the
trigeminal nerve endings located in the cornea,
lacrimal gland and conjunctiva 4 . In isolation and
with other hormones (including neuropeptide Y,
gene-related peptide, insulin-like growth factor
1 and vasoactive-intestinal peptide) substance
P plays a crucial role in wound healing while
providing maintenance and nutrition to the
cornea by promoting the migration, proliferation
and differentiation of corneal epithelial cells.
In diabetes, substance P levels decrease,
contributing to poorer wound healing and
increased susceptibility to corneal neurotrophic
ulcers, due to decreased epithelial migration 5 .
This finding has been confirmed in a recent
pilot study by Markoulli et al (see p38). which
compared patients with diabetes to a healthy
control group 5 . Substance P also decreases in
spinal fluid and the peripheral nervous system
which plays an important role in causing
diabetic peripheral neuropathy 6 . Evidently,
diclofenac decreases the levels of Substance P in
the tear film, something one might want to take
into account when using Voltaren eye drops in
patients with diabetes 7 . Substance P and insulin
growth factor-1, however, reportedly show
good efficacy in healing neurotrophic diabetic
keratopathy, but these treatment options are yet
to be completely explored.
Where to from here
A number of studies focusing on
neurotransmitters and their potential role
in treating diabetes-associated dry eye are
underway or planned. As well as focusing on
diabetic retinopathy, the leading cause of
blindness in diabetes, significant attention
needs to be paid to DMDES in clinical practice
as it can have a severe effect on quality of life.
The pathogenesis of DMDES, however, remains
elusive and further clinical trials are warranted
and ongoing by different research groups in the
UK, Australia and also Auckland.
We will certainly have more to report on this
interesting topic in next year’s review of dry eye
research in the region.
References
1. Manaviat MR, Rashidi M, Afkhami-Ardekani M, Shoja MR. Prevalence of
dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC
Ophthalmol 2008;8:10.
2. Alves Mde C, Carvalheira JB, Modulo CM, Rocha EM. Tear film and ocular
surface changes in diabetes mellitus. Arq Bras Oftalmol 2008;71:96-103.
3. Nishida T, Inui M, Nomizu M. Peptide therapies for ocular surface
disturbances based on fibronectin–integrin interactions. Progress in retinal
and eye research 2015;47:38-63.
4. Davidson HJ, Kuonen VJ. The tear film and ocular mucins. Veterinary
ophthalmology 2004;7:71-77.
5. Markoulli M, You J, Kim J, et al. Corneal nerve morphology and tear film
substance P in diabetes. Optometry and Vision Science 2017;94:726-731.
6. Marfurt CF, Echtenkamp SF. The effect of diabetes on neuropeptide content
in the rat cornea and iris. Investigative ophthalmology & visual science
1995;36:1100-1106.
7. Yamada M, Ogata M, Kawai M, Mochizuki H, Mashima Y. Topical
diclofenac sodium decreases the substance P content of tears. Archives of
Ophthalmology 2002;120:51-54.
Dr James Slater is a clinical research fellow in the
New Zealand National Eye Centre at the University of
Auckland, where he is focusing on corneal nerves and
diabetes. Dr Stuti Misra is a lecturer and researcher at
the University’s Department of Ophthalmology. Her
research focus includes ocular surface abnormalities
and corneal imaging.
Fig 1. A range of factors lead to nerve damage in diabetes
36 | NEW ZEALAND OPTICS SEPTEMBER 2018

Image modified from "Stern, Beuerman, & Pflugfelder (2004)
Fig 1. Healthy tear film (left) and unstable tear film (right), typically characterised by (A) a
discontinuous lipid layer, (B) a hyperosmolar aqueous layer and (C) reduced mucins and goblet cells
Not all eye drops are created equal!
By Drs Priyanka Agarwal and Ilva Rupenthal
DEFICIENCY IN TEAR film quality and
quantity are often considered key defining
characteristics of dry eye disease (DED).
The complex, dynamic multi-component
structure, which comprises an underlying
aqueous-mucous layer and a superficial lipid
layer, synergistically maintains ocular surface
homeostasis. Functionally, the aqueous-mucus
layer is believed to improve the wettability
and support corneal adhesion of the tear film,
while the lipid layer tends to form a superficial
protective “blanket”, providing an occlusive
effect. “Holes” in the blanket (see Fig 1), as
typically observed in evaporative DED and
especially in meibomian gland dysfunction, can
increase exposure of the underlying aqueous
layer of the tear fluid to the environment and
evaporation, leading to hyperosmolarity of the
tear film and epithelial apoptosis. Consequently,
artificial tears are frequently used for the
management of tear film deficiencies. However,
the term “artificial tears” is a misnomer as
most products do not mimic the complex
composition of human tears and contrary to
their name, they typically “supplement” rather
than “replace” the tear fluid.
Artificial tear supplements can be isotonic
or hypotonic aqueous eye drops, which may
have additional viscosity building agents
such as carboxymethylcellulose (Refresh,
Allergan), hydroxypropyl guar (Systane, Alcon)
or sodium hyaluronate (Hylo-Forte, AFT
Pharmaceuticals). They typically function by
augmenting the aqueous layer and transiently
reducing tear fluid osmolarity; however, their
effect is generally short-lived due to rapid
drainage and evaporation from the ocular
surface. Osmoprotective agents, such as
trehalose and erythritol (believed to reduce
the concentration of intracellular organic salts
without disturbing cellular macromolecular
components) may also be added to aqueous
eye drops to reduce hyperosmolar stress. On
the other hand, lipid-based eye drops, which
generally contain amphiphilic lipids and/or
surfactants, fortify the tear film lipid layer to
inhibit excessive evaporation.
Lipid-based artificial tear supplements are
generally believed to have a more sustained
effect than non-lipid eye drops and may be
superior in the management of DED, especially
when it is associated with meibomian gland
dysfunction. For instance, instillation of lipidbased
eye drops has shown a significantly
greater improvement in tear film lipid layer
thickness and consequent reduction in tear
evaporation in patients with DED, resulting in
superior prophylactic efficacy on exposure to
desiccating environmental stress 1 .
Consequently, several lipid-based artificial
tear supplements have been developed with
the objective of reducing tear evaporation and
providing long-term relief to patients with dry
eyes. Lipid-based eye drops are most frequently
available in the form of oil-in-water emulsions
such as Cationorm (Santen SAS) or ointments
such as VitA-POS (AFT Pharmaceuticals).
Liposomal sprays such as Optrex ActiMist
(Optima Pharmazeutische), which potentially
improve tear film integrity by replenishing
the phospholipid layer at the aqueouslipid
interface, have also shown significant
improvement in tear film quality 2 .
A significant concern with long-term eye
drop use, however, is the presence of irritating
preservatives, which can compromise the
ocular surface and worsen patient discomfort.
Surfactants typically used to prepare oil-inwater
lipid-based eye drops may also exacerbate
dry eye symptoms by transiently destabilising
the tear film. Consequently, several surfactants
have been listed in the TFOS DEWS II
iatrogenic report as agents that potentially
cause dry eye 3 . In an attempt to avoid such
components, a preservative-free lipid layer
stabilising eye drop has recently been developed
by Novaliq using a novel, optically transparent,
non-aqueous, semifluorinated alkane. This
product is currently marketed as EvoTears
(Ursapharm) in Europe and as NovaTears
(AFT) in Australia and New Zealand and has
shown promising results in multi-centre clinical
trials performed in patients with evaporative
dry eye disease 4 . Recent research has also shown
that semifluorinated alkanes can be used as a
vehicle for delivery of therapeutic agents to the
eye 5 and potentially simplify the dosage regimen
for patients with chronic dry eye disease.
References
1. Gokul A, Wang MTM, Craig JP. Tear lipid supplement prophylaxis against
dry eye in adverse environments. Contact Lens and Anterior Eye. 2017.
2. Craig JP, Purslow C, Murphy PJ, et al. Effect of a liposomal spray on the preocular
tear film. Contact Lens and Anterior Eye. 2010;33(2):83-7.
3. Gomes JAP, Azar DT, Baudouin C, et al. TFOS DEWS II iatrogenic report.
The Ocular Surface. 2017;15(3):511-38.
4. Steven P, Scherer D, Krösser S, et al. Semifluorinated Alkane Eye Drops for
Treatment of Dry Eye Disease--A Prospective, Multicenter Noninterventional
Study. Journal of Ocular Pharmacology and Therapeutics. 2015;31(8):498-
503.
5. Agarwal P, Scherer D, Günther B, et al. Semifluorinated alkane based systems
for enhanced corneal penetration of poorly soluble drugs. International
Journal of Pharmaceutics. 2018;538(1):119-29.
Dr Priyanka Agarwal is currently a research fellow in the
University of Auckland’s School of Pharmacy. Her research
interests include drug delivery and bench-to-bedside
formulation development. Dr Ilva Rupenthal is a senior
lecturer in the University of Auckland’s Department of
Ophthalmology and director of the Buchanan Ocular
Therapeutics Unit (www.botu.nz), which aims to translate
ocular therapeutic-related scientific research into the
clinical setting. Disclosure: Dr Agarwal’s doctoral studies,
supervised by Dr Rupenthal, were funded by Novaliq GmbH,
manufacturer of NovaTears.
WWW.EYEONOPTICS.CO.NZ | 37

DRY EYE 2018
Trans-Tasman dry eye research collaborators Dr Maria Markoulli, Dr Stuti Misra, A/Prof Jennifer Craig and Dr Laura Downie at ARVO 2018
The immune system, the nervous system
and the ocular surface
By Drs Maria Markoulli, Luisa Colorado and Katie Edwards
A CHARACTERISTIC OF dry eye disease (DED)
is the presence of inflammation, a significant
driving factor of the vicious circle that is
DED. TFOS second dry eye workshop (TFOS
DEWS II) aptly described this process as being
initiated by evaporative water loss leading to
hyperosmolar tissue damage. This contributes
to the inflammatory cascade, with an increased
presence of inflammatory markers in the
tear film, such as matrix metalloproteinase-9
(MMP-9)¹. These changes cause damage to
both epithelial and goblet cells, manifesting in
the clinical signs of corneal and conjunctival
staining and reduced tear break-up time. This
further feeds into the initial hyperosmolarity,
perpetuating the process². This cycle of events
also causes damage to the corneal nerves³
which provide nutritional support to the corneal
epithelium by releasing factors important for
growth and wound healing, such as substance
P⁴. Epithelial cells reciprocate by providing
support to corneal nerves by secreting growth
factors that promote nerve growth⁴. In DED, the
equilibrium of these supporting growth factors
and inflammatory markers is affected.
A possible relationship has been described
between the ocular surface immune and
nervous systems⁵. To understand what impact
DED has on these systems, it is important to
first understand what is normal in the healthy
eye. This can help us understand what we need
to do to maintain the equilibrium of the ocular
surface. To do this, we set out to understand the
relationship between corneal nerve structure
and the presence of inflammatory mediators
and neuromediators in the tear film. We
collected the tears of 21 healthy participants
and also took images of their corneal nerves
using an in vivo corneal confocal microscope.
We found that neuromediator substance P in
the tear film correlated with measures of nerve
fibre morphology, where higher levels were
associated with a greater number of nerves.
We also found that higher levels of tissueinhibitor
of MMPs (TIMP-1) and the inflammatory
mediator interleukin-6 (IL-6) were associated
with a reduced presence of corneal nerves.
These results confirm the immune and nervous
systems in the ocular surface are interlinked and
that what affects one, may affect the other.
Another exciting finding from our research was
that a higher number of hours spent sleeping
meant a higher number of corneal nerves being
present, and more hours spent exercising was
associated with thicker corneal nerves. This
reinforces the need for a greater understanding
into the impact that exercise and sleep have on
the nervous system and the impact that such
modifiable factors might have on ocular health.
With the understanding of the healthy ocular
surface, we can now look towards understanding
how this changes in DED and work towards
restoring its equilibrium.
References
1. Chotikavanich, S, CS de Paiva, Q Li de, JJ Chen, F Bian, WJ Farley and SC
Pflugfelder (2009). “Production and activity of matrix metalloproteinase-9
on the ocular surface increase in dysfunctional tear syndrome.” Invest
Ophthalmol Vis Sci 50(7): 3203-3209.
2. Bron, AJ, CS de Paiva, SK Chauhan, S Bonini, EE Gabison, S Jain, E Knop,
M Markoulli, Y Ogawa, V Perez, Y Uchino, N Yokoi, D Zoukhri and DA
Sullivan (2017). “TFOS DEWS II pathophysiology report.” Ocul Surf 15(3):
438-510.
3. Belmonte, C, JJ Nichols, SM Cox, JA Brock, CG Begley, DA Bereiter, DA
Dartt, A Galor, P Hamrah, JJ Ivanusic, DS Jacobs, NA McNamara, MI
Rosenblatt, F Stapleton and JS Wolffsohn (2017). “TFOS DEWS II pain and
sensation report.” Ocul Surf 15(3): 404-437.
4. Muller, LJ, CF Marfurt, F Kruse and TM Tervo (2003). “Corneal nerves:
structure, contents and function.” Exp Eye Res 76(5): 521-542.
5. Cruzat, A, D Witkin, N Baniasadi, L Zheng, JB Ciolino, UV Jurkunas, J
Chodosh, D Pavan-Langston, R Dana and P Hamrah (2011). “Inflammation
and the nervous system: the connection in the cornea in patients with
infectious keratitis.” Invest Ophthalmol Vis Sci 52(8): 5136-5143.
Dr Maria Markoulli is an optometrist and senior
lecturer at the University of New South Wales School
of Optometry and Vision Science. Dr Luisa Colorado is
a post-doctoral research fellow and Dr Katie Edwards a
lecturer at the School of Optometry and Vision Science
at the Queensland University of Technology.
38 | NEW ZEALAND OPTICS SEPTEMBER 2018

VR to tackle work DED?
By Dr Philip Turnbull
THE MODERN WORKPLACE is a
hostile environment for a dry eye sufferer.
Computer use decreases blink frequency and
completeness, leading to lipid layer breakdown
and increased aqueous tear evaporation, while
air-conditioned office environments frequently
further aggravate the disrupted tear film.
As an academic, I spend a large part of
my day in front of a computer and I am not
immune to the feeling of tired, gritty eyes at the
end of the day. When developing applications
for virtual reality (VR), however, my eyes
felt some relief. To explore this, optometry
student Joyce Wong joined Associate Professor
Jennifer Craig and me in the Ocular Surface
Laboratory at the University of Auckland to
complete a summer studentship, investigating
whether the use of VR can influence the tear
film. Participants attended two visits that were
randomised in order: one where they used a
desktop computer; and another where they
wore a VR headset. Within the VR headset we
projected a ‘virtual desktop’, which meant an
image of the real desktop monitor could be
seen and used within the headset, like a movie
projecting onto a cinema screen. A battery
of dry eye tests were performed before and
immediately after 40 minutes of computer use.
There was little change in the temperature
and relative humidity during the desktop
condition, but there was a significant increase
in the temperature of the air within the VR
headset (from the ambient 22°C to 31°C),
which warmed the anterior eye by 0.6°C. This is
hypothesised to have increased meibum output
as the lipid layer thickness was, on average,
almost one grade higher after VR, whereas
thinning of the lipid layer was observed after
desktop use. This translated to a functional
change in tear film quality, such that the tear
breakup time increased by about three seconds
following VR use while it decreased by three
seconds after desktop viewing.
VR headsets also offer other advantages, like
shifting the focal plane towards the distance
so that only distance spectacle prescriptions
need to be worn and no accommodation is
required and the ability to transform the work
environment to somewhere more pleasant,
perhaps a mountaintop or beach.
The promising results of our study,
combined with improvements in virtual reality
By providing a heated microenvironment, VR headsets may
improve the comfort of computer use for dry eye sufferers
technologies and ergonomics, suggest VR may
become a viable option for dry eye suffers who
are otherwise unable to use a computer.
Dr Philip Turnbull is a lecturer in the School of
Optometry and Vision Science at the University of
Auckland. His research involves developing new tools
using technology such as eye tracking and virtual reality
to investigate visual function.
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WWW.EYEONOPTICS.CO.NZ | 39

DRY EYE 2018
So you want to set up a dry eye clinic?
By A/Prof Jennifer Craig
IT’S BECOME CLEAR, as
our knowledge has evolved,
that dry eye management, if
performed thoroughly, cannot
be squeezed into a normal
examination as part of a standard
eye examination. You wouldn’t
expect to perform a full glaucoma
work-up within a standard
eye examination and neither
should you expect to perform a
detailed dry eye assessment in
this time. This specialised area
requires time, dedicated staff
and an individualised approach,
in the development of the final
management plan.
Preliminary testing
The TFOS DEWS II diagnostic
process leads us through the most
important features of a dry eye
assessment 1 . The first critical
component is history-taking
as this allows the clinician to
develop an understanding of the
individual presenting patient. In a
symptomatic patient, the clinician
must first establish that dry eye
is the most likely problem. This
requires a triaging process, to
help differentiate dry eye from
other underlying causes of ocular
surface discomfort, such as allergy
or infection. Having the patient
answer such triaging questions,
with the aid of a questionnaire
either prior to their appointment
or via an interview with the
assistance of ancillary staff, before
diagnostic testing takes place
can help streamline the process,
especially when it comes to
recording successes and failures
of previous dry eye treatment
attempts. The same is true in
determining relevant risk factors.
A pre-attendance checklist will
allow key information to be passed
to the clinician about possible dry
eye aetiologies and modifiable risk
factors, that will allow for more
focused history-taking on site and
can be addressed as appropriate
within the management plan.
TFOS DEWS II recommends
using one of two validated
questionnaires for evaluating the
symptoms component of a dry
eye diagnosis: the Ocular Surface
Disease Index (OSDI) and the
five-item Dry Eye Questionnaire
(DEQ-5). One or other should be
chosen, noting the appropriate
cut-off for a positive score for each.
Adopting the same questionnaire
within any one practice is advisable
to facilitate monitoring even if the
patient sees a different practitioner.
The symptom recording, like the
triaging and risk factor assessment,
can be undertaken prior to
attendance but is ideally completed
in the waiting room immediately
before consultation as symptoms
are best recorded on the same day
as the clinical signs are evaluated.
Clinical testing
Dry eye can be diagnosed with
instrumentation ranging from
the slit lamp that’s available in
every clinical practice, through to
complex standalone equipment
such as the Keratograph 5M
(Oculus) or TearScience Lipiview
II (Johnson & Johnson). A variety
of other standalone devices and
slit-lamp-mounted instruments
offer diagnostic capabilities
somewhere in between. The
instrumentation available for
clinical testing in any individual
practice will dictate the order
in which testing should be
Clinical
parameter
Basic testing
Advanced testing
Symptoms OSDI or DEQ-5 OSDI or DEQ-5
Global testing
Subtype testing
for aqueous
deficiency
Subtype testing
for evaporative
dry eye
1. Stability testing with minimal
fluorescein
2. Osmolarity may be unavailable
3. Fluorescein and lissamine green
staining of cornea, conjunctiva and lid
margin
Tear meniscus height (slit lamp estimate)
Phenol red thread (moderately invasive)
Schirmer test (useful when applied
without anaesthetic only for confirming
severe aqueous deficiency, as highly
invasive test)
1. Lid margin assessment (thickening,
rounding, notching, telangiectasia,
capped orifices, etc.)
Table 1. Standard and advanced tests for DED diagnosis
performed. Tests must be
conducted the same way each time,
and ordered from least invasive
to most invasive to minimise
the effect of reflex tearing on
subsequent test results.
Encompassing as many of the
global tests that contribute to a
diagnosis of dry eye (according
to TFOS DEWS II) as possible is
ideal – along with symptoms: at
least one positive result from tests
for tear film stability, osmolarity,
and ocular surface staining is
needed to make a diagnosis.
Conducting additional tests for
subtyping is also important as this
helps confirm whether the dry eye
is primarily aqueous-deficient or
evaporative in nature (see Table 1).
The move towards more
non-invasive and objective
testing of the tear film may mean
well-trained ancillary staff could
perform (although not interpret)
parts of the assessment, rather
than the clinician themselves.
Interpretation of the combined
set of results (the more tests, the
better) by the clinician should
2. Lash assessment for madarosis, poliosis,
misdirection, crusting and cylindrical
collarettes
3. Diagnostic gland expression performed
digitally to evaluate meibum
expressibility and quality
be used to inform the patient’s
tailored management strategy.
Management strategies
Consideration must be given to the
treatments and recommendations
that will be offered to patients who
are diagnosed with dry eye disease
(DED). Artificial tear supplements
remain the mainstay of treatment,
but therapies that address both
evaporative as well as aqueousdeficient
subtypes of dry eye need
to be considered (see other articles
in this feature). This may involve
stocking lipid supplements, lid
hygiene products, including those
that tackle Demodex infestation,
and microwaveable wheat or bead
bags for warm compress therapy,
through to offering punctal
plugging for aqueous deficiency
or advanced treatments such as
IPL (intense pulsed light) therapy
and LipiFlow for evaporative dry
eye associated with meibomian
gland dysfunction. Offering
other in-practice therapies
such as BlephEx to remove
crusting associated with anterior
blepharitis (see article, p29),
1. Non-invasive tear film stability
assessment (using reflected mires)
2. Osmolarity testing
3. Fluorescein and lissamine green staining
of cornea, conjunctiva and lid margin
Tear meniscus height quantified digitally
from infrared imaging (IR minimises risk of
reflex tearing)
1. Lid margin assessment (as for basic
testing, plus infrared meibography)
2. Lash assessment (as for basic, plus
epilation for Demodex evaluation under
100x light microscopy)
3. Diagnostic gland expression for meibum
expressibility and quality performed with
Korb Meibomian Gland Evaluator
4. Lipid layer interferometry
40 | NEW ZEALAND OPTICS SEPTEMBER 2018

SOVS’ dry eye clinic opens
By Dr Geraint Phillips
OPTOMETRISTS ARE BECOMING
increasingly aware of the
challenges facing dry eye
patients. Compliance with home
treatments for dry eye can be
variable and patient adherence
to treatment instructions tend to
diminish following an enthusiastic
start. The recent TFOS DEWS II
report provides excellent current
information about the diagnosis
and management of dry eye.
With this in mind, the University
of Auckland School of Optometry
and Vision Science (SOVS) is
planning to establish a dry eye
clinic which will be open to referrals
from community optometrists.
The clinic will be well equipped,
and its aim will be to expose our
final year optometry students to
evidence-based, best practice dry
eye care. This in turn will give our
new graduates the confidence to
take their skills and knowledge
into practice to ensure the public
receives world-class care in this
field. As well as providing detailed
diagnoses and recommendations for
home therapies, a range of in-office
treatments will also be available.
We are very fortunate to have
Associate Professor Jennifer Craig
as our advisor and the clinic will
be led by Dr Marcy Tong, a SOVS
professional teaching fellow who
already has significant experience
in diagnosing and manging dry
eye disease. To attract referrals and
maximise student exposure to dry
eye cases, we will endeavour to set
fees for this service at a level that
will allow access by all patients who
might benefit.
Planning for this clinic is now well
underway and SOVS will announce
more details in the coming months.
The start date will be the beginning
of March 2019.
We look forward to offering
comprehensive dry eye care
to the patients of community
optometrists while at the same
time providing research-led, first
class teaching to our students.
Dr Geraint Phillips, clinic director,
University of Auckland School of
Optometry and Vision Science
Ed’s note: In separate news, the
University of New South Wales
School of Optometry and Vision
Science (SOVS) announced it has
newly launched a dry eye clinic
which it hopes will become a statewide
referral centre for the diagnosis,
imaging and management of the
disease.
diluted tea tree oil application
for Demodex eradication (see Eye
on Ophthalmology, overleaf), lid
margin debridement to manage
excess lid margin keratinisation
and therapeutic gland expression
to relieve meibomian gland
blockage might also be considered.
Eye care professionals are
assuming greater responsibility
than ever in addressing their
patients’ needs through more
targeted management of dry eye.
Whether in a specialist practice
offering a dedicated ‘Dry Eye
Clinic’ or in a general practice,
the commitment to following
consensus recommendations
in diagnosing and managing
dry eye will offer consistency to
patients and help advance our
understanding of the disease. This,
in turn, will improve the care we
can offer to the increasing number
of affected patients. Recognising
risks and limitations in dry
eye and ocular surface disease
management, however, remains
critical. Patients with significant
corneal involvement continue to
require ophthalmological review
and those with a neuropathic
component to their ocular surface
condition might benefit from
referral to a pain clinic for the most
appropriate care, so having suitable
referral options for particularly
complex cases is advisable.
Reference
1. Wolffsohn JS et al. TFOS DEWS II Diagnostic
Methodology report. Ocul Surf 2017; 15(3): 539-74.
Associate Professor Jennifer Craig is
head of the Ocular Surface Laboratory
at the University of Auckland, vice-chair
of TFOS DEWS II and clinical editor of NZ
Optics’ annual special feature on dry eye.
86%
Treat
MGD has been shown
to affect 86% of
patients with dry eye 1
INDICATIONS FOR USE: The LipiFlow System is intended for the application of localized heat and pressure therapy in adult patients with chronic cystic conditions
of the eyelids, including Meibomian Gland Dysfunction (MGD), also known as Evaporative Dry Eye or Lipid Deficiency Dry Eye. CONTRAINDICATIONS:
Do not use the LipiFlow System in patients with the following conditions. Use of the device in patients with these conditions may cause injury. Safety and effectiveness
of the device have not been studied in patients with these conditions.•Ocular surgery within prior 3 months, including intraocular, oculo-plastic, corneal or
refractive surgery procedure•Ocular injury within prior 3 months Ocular herpes of eye or eyelid within prior 3 months•Active ocular infection (e.g., viral,
bacterial, mycobacterial, protozoan, or fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac, or eyelids including a hordeolum or stye)•Active
ocular inflammation or history of chronic, recurrent ocular inflammation within prior 3 months (e.g., retinitis, macular inflammation, choroiditis, uveitis, iritis, scleritis,
episcleritis, keratitis)•Eyelid abnormalities that affect lid function (e.g., entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis,
severe ptosis)•Ocular surface abnormality that may compromise corneal integrity (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial
defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy) PRECAUTIONS: The Activator or Activator II (Disposable) may not fit all eyes,
such as eyes with small palpebral fornices. Use of the LipiFlow System in patients with the following conditions may result in reduced treatment effectiveness
because these conditions may cause ocular symptoms unrelated to cystic meibomian glands and require other medical management. Safety and effectiveness
of the device have not been studied in patients with these conditions.•Moderate to severe (Grade 2-4) allergic, vernal or giant papillary conjunctivitis•Severe
(Grade 3 or 4) eyelid inflammation(e.g., blepharochalasis, staphylococcal blepharitis or seborrheic blepharitis). Patients with severe eyelid inflammation should
be treated medically prior to device use•Systemic disease conditions that cause dry eye(e.g., Stevens-Johnson syndrome, vitamin A deficiency, rheumatoid
arthritis, Wegener’s granulomatosis, sarcoidosis, leukemia, Riley-Day syndrome, systemic lupus erythematosus, Sjögren’s syndrome)•Taking medications known
to cause dryness (e.g., isotretinoin (Accutane ® ) and systemic antihistamines)•Esthetic eyelid and eyelash procedures (e.g., blepharoplasty, lash extensions,
eyelid tattooing). In addition, the treatment procedure may loosen previously inserted punctal plugs, which may worsen the patient’s dry eye symptoms.
Reference: 1. Lemp, M. A., Crews, L. A., Bron, A. J., Foulks, G. N., & Sullivan, B. D. (2012). Distribution of Aqueous-Deficient and Evaporative Dry Eye in a
Clinic-Based Patient Cohort. Cornea, 31(5), 472-478. doi:10.1097/ico.0b013e318225415a. Australia: AMO Australia Pty Ltd, 1-5 Khartoum Road, North
Ryde, NSW 2113, Australia. Phone: 1800 266 111. New Zealand: AMO Australia Pty. Ltd. 507 Mount Wellington Hwy, Mount Wellington, Auckland 1060,
New Zealand. Phone: 0800 266 700.| PP2018TS4191
WWW.EYEONOPTICS.CO.NZ | 41

DRY EYE 2018
EYE ON OPHTHALMOLOGY
FOR ALL EYE CARE PROFESSIONALS
Antiparasitic efficacy of eyelid cleansers for
the treatment of Demodex blepharitis
By Dr Michael Wang and A/Prof Jennifer Craig
Ocular surface infestation with Demodex
mites is recognised as a significant risk factor
for the development of chronic blepharitis 1 .
Although 50% tea tree oil (Melaleuca
alternifolia) is currently the mainstay for
anti-demodectic treatment, it can cause
considerable ocular irritation, restricting its
use to brief in-office application 2 .
This article briefly reviews the relationship
between ocular Demodex and blepharitis,
as well as two recent studies conducted by
the University of Auckland Ocular Surface
laboratory exploring the anti-demodectic
efficacy of commercially-available eyelid
cleansers and manuka honey 3,4 .
Ocular Demodex and blepharitis
Blepharitis is among the most commonly
encountered ophthalmic conditions in
clinical practice, affecting up to 47% of
patients presenting to eye care practitioners.
The condition is characterised by chronic
inflammation of the eyelids and is recognised
to have profound impacts on ocular comfort,
vision and quality of life. It is commonly
associated with signs and symptoms of
ocular surface irritation, dry eye syndrome,
intermittent visual disturbance, conjunctival
hyperaemia, palpebral erythema and eyelid
crusting. In severe cases, the inflammatory
processes can also contribute to the
development of irreversible sight-threatening
corneal damage 5,6 .
Although the complex pathophysiological
mechanisms underlying the development of
chronic blepharitis are not fully understood,
Fig 1. Cylindrical collarettes suggestive of Demodex
recent research would suggest that ocular
infestation with Demodex might be an
important cause. Indeed, ocular demodicosis is
observed in up to 68% of patients with chronic
blepharitis and 60% of those with meibomian
gland dysfunction, the most common subtype of
posterior blepharitis. Infestation with Demodex
folliculorum and Demodex brevis species (Fig
1), predominantly in the eyelash follicles and
meibomian glands respectively, is thought to
trigger an over-activation of host immune and
inflammatory responses through a number of
different mechanisms. Mechanical obstruction
of the eyelash follicles and meibomian glands,
as well as direct consumption and physical
damage of the epithelium by the sharp
appendages of the Demodex mites can directly
induce inflammatory cascades. The associated
reduction in the quality and quantity of
meibomian gland secretions may also exacerbate
aqueous tear evaporation, leading to tear film
instability, hyperosmolarity, and ocular surface
inflammation. In addition, chitin (the main
constituent of the Demodex exoskeleton),
as well as mite break-down products are
strongly antigenic in some individuals. Finally,
Demodex mites are also a potential vector
for bacteria, especially Bacillus oleronius, and
ocular infestation can contribute to bacterial
hypercolonisation of the eyelids 7-9 .
The diagnosis of ocular demodicosis is
usually made clinically by the pathognomonic
observation of cylindrical eyelash collarettes
under slit lamp bio-microscopy (Fig 2), although
the examination of epilated eyelashes for the
presence of mites under light microscopy
remains the gold standard diagnostic test.
Treatment with 50% tea tree oil is the
current mainstay for demodectic blepharitis
management, although the considerable ocular
irritation triggered by topical application limits
its use to brief in-office application periods
of less than 30 minutes. Self-administered
eyelid cleansing formulations containing lower
concentrations are usually recommended for
patient use during intervening periods. The
anti-demodectic efficacy of tea tree oil is thought
to be primarily mediated by its terpinen-4-ol
constituent, although the exact mechanisms by
which inhibition of Demodex viability occurs
has not yet been fully established 1,2,10-12 .
Anti-demodectic efficacy of commercial
eyelid cleansers
A number of dedicated eyelid cleansing
formulations are available commercially and
are marketed to facilitate ocular hygiene
in the management of chronic blepharitis.
However, the antiparasitic efficacy of these
topical formulations has not been previously
established. A recent in vitro study conducted
by the University of Auckland Ocular Surface
Laboratory compared the anti-demodectic
activity of four commercially available dedicated
eyelid cleansers (Cliradex towelette cleanser,
Oust Demodex cleanser, Blephadex eyelid
foam and TheraTears SteriLid eyelid cleanser)
with 50% tea tree oil. The study also sought to
identify and quantify the active antiparasitic
constituents of the commercial formulations 3 .
Consistent with the results of earlier studies,
potent antiparasitic activity of undiluted
terpinen-4-ol was observed against ocular
Demodex mites acquired from epilated eyelashes
of blepharitis patients. Interestingly, linalool, a
42 | NEW ZEALAND OPTICS SEPTEMBER 2018

Professors Charles McGhee
& Dipika Patel, series editors
constituent of TheraTears SteriLid, was found to
exhibit comparable anti-demodectic efficacy to
terpinen-4-ol in its undiluted form. The specific
antiparasitic activity of linalool against ocular
Demodex has not been previously described
in the literature and this novel finding would
support future clinical studies exploring the
efficacy of linalool-based formulations in the
management of demodectic blepharitis.
Although anti-demodectic activity was
demonstrated by all four commercial eyelid
cleansers, the Cliradex towelette cleanser
was the only formulation that demonstrated
comparable antiparasitic efficacy to 50% tea tree
oil. This was thought to be potentially related to
Cliradex containing the highest terpinen-4-ol
content among the commercial formulations.
Anti-demodectic efficacy of manuka
honey
Natural honey is well known for its antiinflammatory
and antimicrobial capacities,
which is likely attributed to its low pH, high
Consistent with the results of earlier
studies, potent antiparasitic activity
of undiluted terpinen-4-ol was
observed against ocular Demodex
mites acquired from epilated
eyelashes of blepharitis patients.
osmolarity hydrogen peroxide content, and nonperoxide
constituents, including methylglyoxal.
New Zealand native manuka (Leptospermum
scoparium) honey, in particular, has gained
significant interest in recent years, due to its
high concentrations of methylglyoxal, which is
recognised to be more resistant to inactivation
Fig 2. Adult Demodex brevis
by heat and catalases then antimicrobial
peroxide constituents. A cyclodextrincomplexed
microemulsion formulation of MGO
manuka honey has recently been developed
for overnight topical eyelid application and is
currently under investigation with regard to
its to ocular hygiene potential in the clinical
management of blepharitis. The eyelid cream
has been observed to exhibit manuka honey
in vitro anti-bacterial activity against ocular
microbiota and successfully underwent
safety and tolerability testing in a two-week
randomised masked clinical trial of healthy
human participants 13,14 .
The in vitro anti-demodectic activity of
MGO manuka honey was compared with
50% tea tree oil in a recently published study
conducted by the University of Auckland Ocular
Surface Laboratory 4 . The findings demonstrated
that cyclodextrin-complexed manuka honey
exhibited comparable antiparasitic efficacy to
50% tea tree oil against ocular Demodex mites
acquired from blepharitis
patients. Together with the
results from the earlier clinical
tolerability trial, this would
suggest that manuka honey
shows the potential to offer
an alternative non-irritating
topical treatment to 50% tea
tree oil. Clinical trials exploring
the efficacy of manuka honey
in demodectic and nondemodectic
blepharitis are
already underway.
Conclusions
Ocular surface infestation with
Demodex mites is emerging as a
significant cause of chronic blepharitis. Topical
50% tea tree oil formulations are the current
mainstay of treatment for demodectic blepharitis,
although the significant ocular irritation restricts
its use to brief application periods under
clinical supervision. A recent study conducted
by the University of Auckland Ocular Surface
Laboratory demonstrated antiparasitic activity
of four commercially available, dedicated eyelid
cleansers, although among the formulations
tested, only Cliradex exhibited comparable
efficacy to 50% tea tree oil. A separate study
showed that comparable anti-demodectic
activity was observed between MGO manuka
honey and 50% tea tree oil, which would suggest
promise for complexed manuka honey to offer
an alternative non-irritating topical treatment for
ocular Demodex infestation.
References
1. Nicholls SG, Oakley CL, Tan A, Vote BJ. Demodex species in human
ocular disease: new clinicopathological aspects. Int Ophthalmol.
2017;37(1):303-312.
2. Koo H, Kim TH, Kim KW, Wee SW, Chun YS, Kim JC. Ocular Surface
Discomfort and Demodex: Effect of Tea Tree Oil Eyelid Scrub in Demodex
Blepharitis. J Korean Med Sci. 2012;27(12):1574-1579.
3. Cheung IMY, Xue AL, Kim A, Ammundsen K, Wang MTM, Craig JP.
In vitro anti-demodectic effects and terpinen-4-ol content of commercial
eyelid cleansers. Contact Lens Anterior Eye. 2018 (in press).
4. Frame K, Cheung IMY, Wang MTM, Turnbull PR, Watters GA, Craig JP.
Comparing the in vitro effects of MGO Manuka honey and tea tree oil on
ocular Demodex viability. Contact Lens Anterior Eye. 2018 (in press).
5. Duncan K, Jeng BH. Medical management of blepharitis. Curr Opin
Ophthalmol. Jul 2015;26(4):289-294.
6. Sung J, Wang MTM, Lee SH, Cheung IMY, Ismail S, Sherwin T, Craig
JP. Randomized double-masked trial of eyelid cleansing treatments for
blepharitis. Ocul Surf. 2018;16(1):77-83.
7. Liu J, Sheha H, Tseng SCG. Pathogenic role of Demodex mites in
blepharitis. Curr Opin Allergy Cl. 2010;10(5):505-510.
8. English FP, Nutting WB. Feeding characteristics in demodectic mites of the
eyelid Aust J Opthalmol. 1981;9(4):311-313.
9. Kim JH, Chun YS, Kim JC. Clinical and Immunological Responses in
Ocular Demodecosis. J Korean Med Sci. 2011;26(9):1231-1237.
10. Gao YY, Di Pascuale MA, Li W, et al. In vitro and in vivo killing of ocular
Demodex by tea tree oil. Br J Ophthalmol. 2005;89(11):1468-1473.
11. Gao Y-Y, Di Pascuale MA, Elizondo A, Tseng SCG. Clinical Treatment
of Ocular Demodecosis by Lid Scrub With Tea Tree Oil. Cornea.
2007;26(2):136-143.
12. Kheirkhah A, Casas V, Li W, Raju VK, Tseng SC. Corneal manifestations
of ocular demodex infestation. Am J Opthalmol. 2007;143(5):743-749.
13. Craig JP, Rupenthal ID, Seyfoddin A, Cheung IMY, Uy B, Wang MTM,
Watters GA, Swift S. Preclinical development of MGO Manuka Honey
microemulsion for blepharitis management. BMJ Open Ophthalmol.
2017;1(1):e000065.
14. Craig JP, Wang MTM, Ganesalingam K, Rupenthal ID, Swift S, Loh CS,
Te Weehi L, Cheung IMY, Watters GA. Randomised masked trial of the
clinical safety and tolerability of MGO Manuka Honey eye cream for the
management of blepharitis. BMJ Open Ophthalmol. 2017;1(1):e000066.
Dr Michael Wang is a part-time
PhD student in the Department
of Ophthalmology at the
University of Auckland, under
the supervision of A/Prof
Jennifer Craig.
WWW.EYEONOPTICS.CO.NZ | 43