Dry Eye 2020

nzoptics

and

present…

Dry Eye 2020

l AI for diagnosing MGD

THE

l ECPs’ approach to dry eye

management

l Omega fatty acids for DED

l Preserved of non-preserved, that is

the question?

l Castor oil for blepharitis

l When should you check for dry eye?

APPROACH TO PRESERVATIVE-FREE

DRY EYE CARE

WWW.EYEONOPTICS.CO.NZ | 11


DRY EYE 2020

Celebrating dry eye research, here,

there and everywhere

By Lesley Springall, editor NZ Optics

WELCOME TO OUR sixth dry eye special feature. Dry eye continues

to enthral and engage researchers and eye care practitioners across

the world, spurred on by the work of the Tear Film & Ocular Surface

Society’s second dry eye workshop (TFOS DEWS II) and driven by

people committed to improving the quality of life for the world’s

millions of dry eye disease sufferers.

This year, as well as delving into the ongoing, high-level research

at the University of Auckland’s Ocular Surface Laboratory (OSL),

we’re also pleased to introduce more international contributors, many

of whom work with Associate Professor Jennifer Craig and her OSL

team: California-based, fellow TFOS ambassador, Dr Scott Schachter’s

shares his opinion on whether eye care professionals (ECPs) should

be screening for dry eye with every examination (p40); Melbourne

University’s Dr Laura Downie provides an exciting update about her

team’s new point-of-care test for rapid and accurate dry eye diagnosis,

ADMiER (p30); while Canada’s

Karen Walsh presents her latest

published research into preserved

versus non-preserved eye drops (p26);

and the UK’s Sonia Trave-Huarte and

Prof James Wolffsohn discuss their work

with the OSL and other international collaborators

into ECPs’ approach to dry eye management (p22).

Once again, we are proud to share this latest update on all things

dry eye from this part of the world and further afield to recognise

and celebrate the collaborative efforts ongoing in dry eye today, many

involving the University of Auckland. We would also like to thank the

many contributors to this year’s feature, but especially our wonderful

clinical editor, A/Prof Jennifer Craig, who, with considerable time and

effort on her part, makes this feature possible.

Battling OSD despite the pandemic

By A/Prof Jennifer Craig

NO ONE COULD have imagined what 2020

would bring, least of all those in the eye

professions for whom ‘2020’, by all rights, was

supposed to be our ‘perfect’ year. And yet here

we are, more than six months in, with very

few globally having remained immune to the

impact of SARS-CoV-2.

Closed international borders and grounded

planes have led to ophthalmic conference

cancellations across the world. I pinch myself,

as I struggle to believe I was able to visit

Colombia, (much) earlier this year, to deliver

A/Prof Jennifer Craig conducting OSL research at

Armageddon, Auckland 2020

a TFOS DEWS II live demonstration session

at their annual ophthalmology congress, or

Barcelona where I chaired and presented at

Laboratoires Théa’s Ocular Surface Masterclass

for clinical ophthalmologists. Since then,

there’s been a string of conferences, at which

the Ocular Surface Laboratory (OSL) team

would have been represented, either cancelled,

postponed or rapidly converted into virtual

meetings. These include the Dutch Contact

Lens Congress (NCC) in the Netherlands, the

Scientific and Educators’ Meeting in Optometry

(SEMO) in Auckland, the Association for

Research in Vision and Ophthalmology

(ARVO) in Baltimore, the European Society

of Cataract and Refractive Surgery (ESCRS)

in Amsterdam and the American Academy

of Optometry (AAOptom) in Nashville,

Tennessee, to name but a few.

For those of us in the field of ocular surface

research, however, the most heart-breaking

of all was the cancellation of the muchanticipated,

quadrennial TFOS Conference.

Due to have been held in Italy in September,

this meeting provides the opportunity for

clinician and basic science researchers,

educators and industry representatives to

network, discuss advances in the ocular

surface disease (OSD) field and plan future

research that will ultimately benefit patients.

We all look ahead to better times when we

can meet again and, personally, I also look

forward to the opportunity of fulfilling the

incredible honour of delivering the seventh

Claes H Dohlman plenary lecture on Ocular

Surface Disease as a Lifestyle Epidemic. In

the meantime, we will do our best to face

the challenges presented by the pandemic in

continuing to provide and promote better

health for patients with OSD.

OSL team update

For the Ocular Surface Laboratory, the pace

of life, somewhat paradoxically, stepped up

a notch during lockdown, and the adaptive

leadership challenge I had set myself for

reimagining ocular surface research without

face-to-face contact became more of a living

reality than a hypothetical scenario. I’m

incredibly proud of the resilience, agility

and adaptability of the OSL team, who

worked hard with each other, and with our

stakeholders, to reshape our research into a

series of viable projects capable of respecting

social distancing restrictions.

The researchers who were perhaps most

immediately affected by Covid-19 restrictions

were our two six-month visiting scholars: PhD

student Samira Hassanzadeh from Iran and

Sebastian Golcyzk, a masters student from

Germany, who, although they were thwarted

in their plans to explore our beautiful country,

rallied professionally with the support of the

OSL team to produce some great research

outcomes during their time with the OSL.

The projects they worked on are described

on pages 14 and 20, respectively, and we

look forward to welcoming them back to

collaborate further and to more extensively

explore New Zealand in the future.

Post-doctoral fellow Dr Alex Müntz has

had a fruitful year with publications expected

to be in double digits this year, including a

number as lead author. Alex plays a key role

in coordinating and supervising the team’s

research and, as a previous proud recipient of

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DRY EYE 2020

an ARVO Science Communication Training

Fellowship, is the OSL’s communications lead,

guiding our online and social media presence.

He’s ably accompanied in his research

endeavours by the team’s other post-doctoral

fellows, Dr Sanjay Marasini and Dr Ally Xue,

both of whom completed their PhDs last year

and have published articles in the Ocular

Surface Journal, ophthalmology’s highest

impact factor journal that accepts original

research, this year.

OSL collaborations

The OSL continues to collaborate widely,

within the University, nationally and

internationally. As well as supporting

Auckland University’s School of Optometry

and Vision Science Dry Eye Clinic (see story

on p22), we value local research collaborations

with Dr Phil Turnbull (p15) and Dr Ehsan

Vaghefi (below) in SOVS, with Associate

Professor Simon Swift in Molecular Medicine

and with the Auckland Bioengineering

Institute.

Outside the university, we collaborate with

optometrists, ophthalmologists, nurses and

medical practitioners in the community. We

continue to work closely with Grant Watters in

Auckland (p34), and together with Dr Graham

OSL: AI for diagnosing MGD

By Samira Hassanzadeh and Dr Ehsan Vaghefi

Wilson, on the Dunedin Multidisciplinary

Health and Development Study (p39).

International collaboration remains key to the

group achieving its aims, with highlights this

year being doctoral student co-supervision in

Australia and the UK, and the opportunity to

contribute, along with Dr Marasini, to two of

the subcommittees of the British Contact Lens

Association’s global Contact Lens Evidencebased

Academic Report (CLEAR) which should

be published in 2021.

We’re also proud to have successfully led

an international multicentre clinical trial,

involving the University of New South Wales

in Australia, the University of Waterloo

in Canada and Aston University in the

UK. The outcome of this trial, which was

awarded significant funding through Alcon’s

investigator-initiated research programme, is

evidence-based guidance that will be valuable

for eye care practitioners in managing patients

with dry eye disease in clinical practice.

With current postgraduate students,

including Dr Michael Wang (p24), well on their

way towards degree completion, the OSL team

has recently expanded to include part-time

researchers: optometrist Ryan Mahmoud,

who is currently completing a University

of Auckland postgraduate certificate; nurse

prescriber Marc Maclean, from Counties

Manukau Health; and SOVS professional

teaching fellow and MSc student Bhavna Patel

(p16).

Having gained New Zealand Health

Research Council (HRC) funding for a

therapeutic dry eye project, currently being

led by Associate Professor Ilva Rupenthal

(p19), we expect to see an additional clinical

PhD student recruited very soon. Karien Nel,

who trained as an optometrist in South Africa,

has also recently joined the OSL as a clinical

researcher on the Azura clinical trial (p43).

This is an exciting new project for the OSL,

complementing a scientific research project

currently underway in collaboration with

Azura and led by Dr Müntz.

As always, dry eye patients who might

be interested in participating in any of our

research projects are encouraged to get in touch

(0800 EYE PAIN) to find out more information

about currently enrolling projects.

Associate Professor Jennifer Craig heads the Ocular

Surface Laboratory in the Department of Ophthalmology

at the University of Auckland, New Zealand, and was

vice-chair of the Tear Film & Ocular Surface Society’s

second dry eye workshop (TFOS DEWS II).

AS THE MAJOR cause of evaporative dry

eye disease¹, meibomian gland dysfunction

(MGD) requires careful assessment in the

clinical setting. Morphological characteristics

of meibomian glands are evaluated by

meibography. This technique yields information

on MG loss by observing the glands under

infra-red illumination as light structures against

a darker background during lid eversion (Fig

1)². The images are then subjectively graded

by clinicians to indicate the severity of MG

drop out, which is clinically important in the

diagnosis and prognosis of MGD. However,

test-retest and inter-observer variabilities in

MG atrophy grading exist³.

Fig 1. Al process of meibography grading

Convolutional neural networks (CNNs)

have shown promise in both classification and

segmentation problems in ophthalmic imaging⁴.

It is of interest to use deep learning methods

to automate the process of evaluating atrophy

in meibography images. Specifically, clinicians

can use such methods to automatically segment

the eyelids and identify areas of gland coverage

in meibography images and then compute the

amount of MG drop out.

Our pilot study involves looking at a set of

821 upper eyelid images that were collected

using the Keratograph 5M (Oculus) and

clinically graded with the Pult score grading

system. We have trained an artificial intelligence

(AI) system on this data, such that we

can now accurately distinguish the

gland area and highlight the drop out

region for the clinician and replicate the

clinical score, all within 10 seconds of

image acquisition.

Telehealth and AI are the fastest

growing health-related fields in the

post Covid-19 era. Ophthalmology and

optometry have been at the forefront

of smart technology adoption in the

past decade⁵. AI enables automated

and standardised clinical screening

to be delivered across the nation with

minimal clinical load. Combining

forces between the Department

of Ophthalmology and the School

of Optometry and Vision Science at the

University of Auckland, our group is aiming

to develop an accurate AI algorithm for MGD

screening, diagnosis and grading.

References

1. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution

of aqueous-deficient and evaporative dry eye in a clinic-based

patient cohort: a retrospective study. Cornea. 2012; 31(5):472-478.

doi:10.1097/ICO.0b013e318225415a

2. Fineide F, Arita R, Utheim TP. The role of meibography in ocular surface

diagnostics: A review. Ocul Surf. Published online May 19, 2020.

doi:10.1016/j.jtos.2020.05.004

3. Arita R, Minoura I, Morishige N, et al. Development of Definitive and

Reliable Grading Scales for Meibomian Gland Dysfunction. Am J

Ophthalmol. 2016; 169:125-137. doi:10.1016/j.ajo.2016.06.025

4. Vaghefi E, Hill S, Kersten HM, Squirrell D. Multimodal Retinal Image

Analysis via Deep Learning for the Diagnosis of Intermediate Dry

Age-Related Macular Degeneration: A Feasibility Study. J Ophthalmol.

2020; 2020:7493419. doi:10.1155/2020/7493419

5. Ting DSW, Pasquale LR, Peng L, et al. Artificial intelligence and deep

learning in ophthalmology. Br J Ophthalmol. 2019; 103(2):167-175.

doi:10.1136/bjophthalmol-2018-313173

Study lead and PhD student,

optometrist Samira Hassanzadeh

is a recent visiting scholar in the

Department of Ophthalmology

at the University of Auckland

and holds a masters in medical

education from Mashad

University.

Dr Eshan Vaghefi is a research

fellow with the Molecular

Vision Lab and Auckland

Bioengineering Institute and a

senior lecturer in physiological

optics at the School of

Optometry and Vision Sciences

at the University of Auckland. He

was responsible for training the

AI system for this study.

14 | NEW ZEALAND OPTICS SEPTEMBER 2020


Simo Zhang, Karyn Zhao, Dr Andy Kim, Dr Phil Turnbull, Dr Akilesh Gokul and A/Prof Jennifer Craig at Armageddon Auckland 2019

OSL: “Let’s play a staring contest!”

By Drs Alex Müntz and Phil Turnbull

IN 2019, YOUNG gamers seemed

like a good proxy to study the

association between extended

screen time, blinking and dry

eye. Armageddon, New Zealand’s

largest gaming convention,

provided an ideal opportunity for

this. With the generous support

of the organisers, optometry

students donned eye-catching

T-shirts and, armed with iPads,

joined the Ocular Surface

Laboratory (OSL) team at

Armageddon 2019 in Auckland.

Attendees were invited to

complete surveys on screen use

habits and ocular discomfort,

while customised software,

developed by collaborators at

Aston University in Birmingham,

England, tracked the user’s

blinking in the background.

Finally, participants completed

a virtual ‘staring contest’ against

the iPad – a previously validated

proxy measurement for tear film

stability¹.

Well before the worldwide

lockdown recalibrated our

concept of ‘extended screen time’,

the reported average daily screen

time of 6.7 ± 3.6 hours seemed

high. While these numbers may

seem meek now, the association

between screen time, blinking

behaviour and dry eye disease

has started to become clearer and

appears particularly concerning

for young patients.

Nearly 500 respondents

aged 13 to 75 provided Dry Eye

Questionnaire 5 (DEQ-5) and

Symptom Assessment in Dry

Eye (SANDE) scores. Based on

symptom scores alone, more than

90% of respondents qualified as

symptomatic of dry eye disease,

while one in three cases also

Longer daily screen and

gaming time were correlated with

suboptimal blinking and poorer

ocular symptomology, akin to

dry eye disease patients

demonstrated reduced tear film

stability. Longer daily screen and

gaming time were correlated with

suboptimal blinking and poorer

ocular symptomology, akin to

dry eye disease patients.

In New Zealand, irrespective

of lockdown status, the increase

in screen time is not a curve that

is expected to flatten anytime

soon. With evidence around

the health effects of screen use

mounting, policymakers are

becoming increasingly attuned

to the need for effective policies

around safe screen use in

youth. This perhaps signifies

an opportunity for eye care

practitioners to get ahead of

the game by integrating ocular

surface screening and educational

advice around screen use in

routine clinical eye practice.

Reference

1. Wolffsohn JS, Craig JP, Vidal-Rohr M, et al.

Blink Test enhances ability to screen for dry eye

disease. Contact Lens Anterior Eye 2018; 41:

421–425.

Dr Alex Müntz is a post-doctoral

research fellow in the OSL, while Dr

Philip Turnbull is a senior lecturer in the

School of Optometry and Vision Science

at the University of Auckland.

WWW.EYEONOPTICS.CO.NZ | 15


DRY EYE 2020

OSL: Ocular surface changes over time

By Bhavna Patel

DRY EYE DISEASE (DED) affects

approximately one in three New Zealanders.

As clinicians, it’s critical that we accurately

diagnose and manage this impactful disease.

Left untreated, DED is detrimental to patients’

quality of life with its impact ranging from

intermittent ocular discomfort to more serious

psychological effects, such as depression.

The TFOS DEWS II report improved

our understanding of DED and identified

knowledge gaps, prompting further research.

For example, we now know that most patients

suffer from an evaporative form of dry eye

and that the disease is perpetuated by entering

a vicious cycle of worsening clinical signs

and symptoms over time. However, our

understanding of the early, or preceding stages

of this cycle, is still relatively limited.

Research from the University of Auckland’s

Ocular Surface Laboratory (OSL) has

significantly advanced our knowledge about the

natural history of dry eye disease, identifying

the order and progression of ocular surface

changes¹ , ². Meibomian gland morphological

features identified in paediatric populations

in this research, indicate an earlier disease

onset than previously thought. To facilitate

better management and prevention strategies

in future, we must seek to improve our

understanding of the onset and evolution of

DED as well as the key risk factors.

For my masters’ project, I will be

undertaking a longitudinal, long-term study of

tear film and ocular surface changes in a cohort

of young participants. Annual assessments

of university students will be conducted and

will include the evaluation of lifestyle factors,

such as diet and screen time, ocular symptoms,

as well as anterior segment assessments. By

identifying the progression of ocular changes

over time, this study is expected to complement

our understanding of the natural history of

DED and contribute to our ability to detect risk

factors earlier.

References

1. Wang MTM, Craig JP. Natural history of dry eye disease: Perspectives

from inter-ethnic comparison studies. Ocul Surf 2019; 1–10.

2. Craig JP, Wang MTM, Muntz A, Lim J, Kim JS et al. Ageing and the

natural history of dry eye disease: a prospective registry-based crosssectional

study. Ocul Surf 2020; in press.

Bhavna Patel is a professional teaching fellow in

the School of Optometry and Vision Science and

part-time MSc student with the OSL at the University

of Auckland.

BCLA dry eye certificate downunder

FOR THE FIRST time, the British Contact Lens

Association’s (BCLA’s) Certificate in Dry Eye and

Contact Lens Retention, will be available

outside of the UK.

The Tear Film and Ocular Surface

Society’s second dry eye workshop

(TFOS DEWS II) vice chair,

Associate Professor Jennifer Craig,

has been approved to lead the first

satellite objective structured clinical

examinations (OSCE) testing site outside

the UK in New Zealand.

Recognised as a game-changer in continuing

education, the BCLA was the first to bring its members

live demonstration TFOS DEWS II lectures in 2017. These now

feature across the world, including within the University of Auckland’s

School of Optometry and Vision Science (SOVS) teaching programme.

Together with fellow TFOS DEWS II steering committee members,

Professors James Wolffsohn and Lyndon Jones, A/Prof Craig (collectively

nicknamed the ‘three musketears’), subsequently joined forces with the

BCLA to develop the dry eye disease (DED) management certificate.

It can be used towards a BCLA fellowship and is designed to support

practitioners’ keen to specialise in DED management.

Comprised of a series of online lectures and

resources, with online assessment and

feedback, it also includes approved

practical workshops for gaining handson

experience in performing the latest

techniques.

“Having the certificate signals

to patients and peers alike, a

practitioner’s dedication and high level

of contemporary knowledge in dry eye,

which can facilitate practice-building in this

specialist area,” said A/Prof Craig, adding how

exciting it is to bring the certificate to practitioners in

Australasia for the first time.

The first New Zealand OSCE, scheduled to be held in parallel with

the SOVS-hosted Scientific and Educators’ Meeting in Optometry

(SEMO) conference in April, fell victim to the impact of the pandemic,

but is expected to be up and running in coming months, said A/

Prof Craig. Those interested in BCLA membership and pursuing a

Certificate in Dry Eye and Contact Lens Retention are encouraged to

check the BCLA website (www.bcla.org.uk) for more details.

16 | NEW ZEALAND OPTICS SEPTEMBER 2020


DRY EYE 2020

OSL: The benefits

of blinking

By Dr Andy Kim

THE IMPACT OF blinking on the quality of the tear film layer has

gained significant attention in recent times¹. Normal apposition of the

upper and lower lids during a complete blink serves to secrete and spread

the meibum adequately over the tear film surface. Any disruption in

the normal blink can, therefore, compromise the stability of the tear

film layer. The increased use of computers has brought about multiple

health concerns, including ocular discomfort. Incomplete and infrequent

blinking are key abnormalities associated with computer use and have

been associated with

dry eye symptoms

and signs.

Recent research

in the Ocular

Surface Laboratory

(OSL) evaluated

the potential

for prescribed

blinking exercises

in retraining and

modifying blink

patterns to alleviate

dry eye symptoms

and improve clinical

signs².

Credit: Dr Andy Kim, OSL, University of Auckland

A cohort of

54 participants

with dry eye symptoms were recruited and instructed to perform a

10-second cycle of blinking exercises (Fig 1) every 20 minutes during

waking hours for four weeks. A total of 41 participants completed

the study, reporting an average of 25.6 daily blinking exercise cycles.

Improvements in dry eye symptoms were noted on DEQ-5 (11±4 to

7±3; p


Tackling the DED vicious circle

A RECENTLY AWARDED Health Research

Council project grant will investigate a novel

eye drop that tackles the vicious circle of dry

eye disease (DED), one of the most common,

yet undertreated, chronic ocular surface

conditions.

Multifactorial in nature, DED can arise from

numerous interrelated underlying pathologies.

Current therapies, however, often address

only a single issue, resulting in suboptimal

treatment outcomes, said investigators, led by

Associate Professor Ilva Rupenthal, director

of the Buchanan Ocular Therapeutics Unit, in

collaboration with Associate Professor Jennifer

Fig 1. Vicious DED circle and project aim

Craig, Dr Stuti Misra and Dr Priyanka Agarwal,

from the University of Auckland. “Moreover,

response to therapy is often slow with adverse

effects from formulation excipients such as

preservatives and surfactants causing further

ocular toxicity upon long-term use, ultimately

worsening DED symptoms.”

This project will investigate the

development of a preservative-free eye drop

that tackles both tear film instability and

ocular surface inflammation, without the

need for further additives, to break the vicious

circle of DED (Fig 1). This will be achieved

by combining the inflammasome inhibitor,

tonabersat, tackling inflammation upstream

of currently used anti-inflammatory drugs,

with a hydrocarbon vehicle able to stabilise

the tear film lipid layer, said A/Prof Rupenthal

who, together with Dr Agarwal, will be

responsible for formulation development and

characterisation, while A/Prof Craig and Dr

Misra will map inflammasome involvement

in DED patients to aid clinical translation.

The research team will be supported by two

PhD students, Santosh Bhujbal and a clinical

researcher who is yet to be appointed, and will

collaborate with the University of Cologne in

Germany to test the developed eye drop in a

A/Prof Jennifer Craig, Dr Stuti Misra and A/Prof Ilva

Rupenthal

pre-clinical model of DED

“We are very excited to get this project

started and develop an eye drop that

tackles underlying inflammation while

also addressing the tear film instability

seen in most DED patients,” said the team.

“DED remains one of the most common,

yet undertreated chronic ocular surface

conditions which negatively impacts the

quality of life of patients. This eye drop has

the potential to narrow the significant gap

between diagnosed and appropriately treated

DED patients in the near future.”

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DRY EYE 2020

OSL: Blink tracking 2.0

By Dr Alex Müntz

IN 2011, WE were taking in five times as

much information each day as we had done 25

years earlier¹, and this was before most people

owned smartphones. Nowadays many of us

spend a majority of our waking hours looking

at or scrolling down screens.

In this fast-paced, visually stimulating

environment, our attention spans have

shortened but, in other ways, have also

increased. “Blink, and you’ll miss it”, has

become our modern-day mantra; and, indeed,

in a literal sense, when we are focused,

we blink less. Screen use can dramatically

reduce the quality of the blink and this may

play a significant role in the expression and

development of dry eye disease² , ³.

On average, we blink 10,000 times per day, or

at least we should, but blink dynamics can vary

significantly depending on the task at hand. The

issue with this textbook value is that it originates

in research largely predating the digital age.

Blinking has almost exclusively been examined

in controlled laboratory settings and this data

may not be representative of natural blinking in

OSL: Preventing DED before it starts

By Drs Sanjay Marasini and Alex Müntz

everyday environments. “Just blink normally,

please”, turns out to be a difficult instruction for

study participants to follow. Our understanding

of true, natural blinking patterns, their diurnal

variation and differences between individuals

is inadequate and, most likely, outdated. Better

methods are needed to track blink dynamics

accurately and unobtrusively.

The solution may come in the form of a

wearable blink tracker, similar to a step counter

or heart rate monitor. Using advanced sensing

technologies positioned close to the eye, such

a device has the potential to provide real-time

monitoring over the course of a day.

To surmount this engineering feat, a

collaboration has recently been established

between the Ocular Surface Laboratory

(OSL) and leading biosensing experts from

the Auckland Bioengineering Institute.

Spearheading the first step has been Sebastian

Golczyk, a visiting master’s student from the

Ernst Abbe University of Applied Sciences in

Jena, Germany. His work, the analysis of which

is currently underway, evaluated the impact on

blinking dynamics of adding the weight of a

sensor to the eyelids.

Blinking is the fundamental mechanism that

protects the ocular surface. Growing realisation

of its role in the associated rise of extended

screen time and dry eye disease, especially in

youth, begs our efforts in establishing a better

understanding of true blinking in modern life.

References

1. Hilbert M, López P. The World’s Technological Capacity to Store,

Communicate, and Compute Information. Science (80- ) 2011; 332: 60

LP – 65.

2. Wang MTM, Tien L, Han A, et al. Impact of blinking on ocular surface

and tear film parameters. Ocul Surf 2018; 16: 424–429.

3. Kim AD, Muntz A, Lee J, et al. Therapeutic benefits of blinking exercises

in dry eye disease. Contact Lens Anterior Eye. Online ahead of print

2020. DOI: 10.1016/j.clae.2020.04.014.

Dr Alex Müntz is a post-doctoral research fellow in the

OSL at the University of Auckland.

THE MODERN WORKPLACE serves as

a catalyst for dry eye disease (DED) and

ocular discomfort for many. Air conditioning,

central heating and extended digital screen

use promote accelerated tear film evaporation

and instability. Previous Ocular Surface

Laboratory (OSL) research has demonstrated

prophylactic benefits from certain artificial

tear supplements, when applied prior to

exposure to an adverse environment¹.

With investigator-initiated research funding

awarded by Alcon Laboratories (Australia) to

A/Prof Jennifer Craig and Dr Alex Müntz, the

prophylactic potential of two Systane products:

a new generation lipid-based eye drop, Systane

Complete; and an established, non-lipid-based

eye drop, Systane Ultra, was explored. The

prospective, double-masked, contralateral,

randomised crossover trial, which has recently

been published in the Ocular Surface journal²,

involved 28 participants. The lipid-based

formulation was randomly allocated to either

the right or left eye and the non-lipid-based

drop to the contralateral eye. Clinical measures

were evaluated in accordance with current

consensus diagnostic criteria for dry eye

disease 3 . Outcomes were compared between

baseline, 10 minutes post-instillation and,

again, 10 minutes post-exposure to a validated

simulated adverse environment that was created

by a standing fan at a distance of 1m for a

period of 2.5 minutes¹. At a subsequent study

visit, the eye drop allocation was switched to

the opposite eye and the process repeated.

Following adverse environment exposure,

participants reported enhanced subjective

comfort with both formulations. Results

indicated that while both eye drops were able

to offer some level of protection, the

lipid-based formulation was associated

with reduced symptoms, improved tear

film stability and better lipid layer quality

(all p


16 TH ANNUAL

OPTOMETRY

CONFERENCE

Your

safety is our

top priority. This

year we will be hosting

an intimate conference of

less than 100 people at our

5 star boutique venue. The

event will be structured to go

ahead within the alert level

we find ourselves working

in. We will also be live

streaming the

event.

Eye Institute are thrilled to

announce our 2020 Annual

Optometry Conference and

Workshop.

Join us for an exciting and informative

weekend of valuable CPD points and

engaging rapid fire presentations. Accompany

your peers in listening to our 15 world class

surgeons speak on the latest techniques and

advancements in ophthalmic treatment. We

are also delighted to announce our guest

speaker for this conference is Sir John Kirwan

who will be sharing his own personal journey

of depression, resilience and hope;; aiding in

our conference theme of facilitating positive

health and wellness in the workplace.

Register now for a highly informative

and inspirational day accompanied

by exceptional food, wine and industry

networking.

Sunday 8.00am - 5.00pm

20th September 2020

Venue:

Mantells Mt Eden

466A Mt Eden Road, Auckland

Register online:

www.eventfinda.co.nz/2020/

eye-institute-annualoptometry-conference-2020/

auckland

Or click

REGISTER

Cost: $90

Live streaming costs: $25

Breakfast, morning tea & lunch

provided. Live guest speaker and

a networking session with wine

and canapes.

Book now for your 2020 CPD Credits

(including Therapeutics).

We are honoured to

present our 2020 guest

speaker, Sir John Kirwan.

Sir John Kirwan (JK) is one of New

Zealand’s favourite former All Blacks.

Playing for our national team for a

decade, he holds the New Zealand

record for the most firstclass rugby

tries. Since retiring from professional

sports he has bravely shared his

personal story of depression, resilience

and hope. His journey has led him to an

active involvement with mental health

awareness campaigns in New Zealand.

JK’s willingness to share his story and

his dedication to this cause has gone

a long way to removing the stigma

that surrounds depression and mental

illness in New Zealand.

Our theme for our annual conference

this year is positive health and

wellness in the workplace, and we

strive to continuously create a culture

that improves and enhances the lives

of our team members.

Contact: professionaleducation@eyeinstitute.co.nz

WWW.EYEONOPTICS.CO.NZ | 21


DRY EYE 2020

ECPs’ approach to dry eye management

By Sonia Trave-Huarte and Prof James Wolffsohn

The TFOS DEWS II reports were published in

2017, bringing practitioners up to date on the

scientific evidence related to dry eye disease

(DED), including our current understanding

of its pathophysiology, a consensus-refined

definition, a more definitive approach to

diagnosis and a review of management

options. However, it also identified a lack of

randomised clinical trials that are important

for informing practitioners about relative

efficacy of available management options

at different levels of disease severity and

across the subclassification spectrum, from

evaporative to aqueous deficiency.

As a starting point in addressing this

gap in knowledge, a cross-sectional study

was designed to establish current practice

norms. An anonymous online questionnaire

was distributed to eye care professionals

around the world. Translated into 14 different

languages, this six-question survey sought to

determine the management and treatment

approaches used by eye care practitioners

(ECPs) worldwide, based on disease severity

and subclassification.

The survey was completed by 1,139 eyecare

professionals (37% ophthalmologists and 58%

optometrists) from 51 countries. It identified

that management varied significantly by

continent and by country (p


wall-mounted screens in addition to our new slit-lamp camera and

video, staff and students can educate patients about the specific causes

of their dry eye. Patients are offered a full range of treatment options

and presented with a step-wise personalised management plan based on

their specific history and clinical findings.”

In alignment with TFOS DEWS II recommendations, Dr Tong

said she trains students to begin by educating the patient about

the chronic nature of dry eye disease and possible environmental

modifications. They then demonstrate lid cleansing, lid massage after

warm compresses, blinking exercises as well as drop and gel instillation,

as required. A direct correlation to the success of treatment has been

observed when a patient has a better understanding of their condition

and complies with home management, she said.

The patient’s dry eye management plan is then re-evaluated at the

next appointment to determine the patient’s progress, so it can be

amended according to the patient’s response, taking into account new

research, treatments or tips as these emerge, said Dr Tong. “At this

stage, the students are able to discuss other available in-office treatment

options such as the Blephasteam with gland expression, BlephEx ‘deep’

lid cleansing, IPL (intense pulsed light) or Lipiflow therapy. The longterm,

follow-up care is recognised to be critical to successful outcomes

and satisfied patients.”

Associate Professor Jennifer Craig, head of the Ocular Surface

Laboratory at the University, has been involved since the clinic’s

inception and has supported its development. She is extremely proud

of the clinic’s work, student training and the expansion of its services,

so more patients, many of whom have suffered with DED for a long

time, can be helped, she said. “It is a fulfilling specialty and a privilege

to watch future eyecare professionals being inspired to learn new

techniques to better manage their patients of the future, as the demand

for dry eye therapy increases.”

Demodex treatment

advances

TP-O3, A TOPICAL ophthalmic

treatment for blepharitis due

to Demodex infestation, has

successfully completed its phase

IIb trial.

Adapted from an established

veterinary medicine, TP-03,

which targets the nervous

Cylindrical eyelash crusting considered

system of the Demodex mite, pathognomonic of Demodex infestation

killing the mites, was found to

be safe and well tolerated. The Mexican research study, published

in Investigative Ophthalmology & Visual Science, included 15 patients

with mild to severe lid margin erythema and an average Demodex

density of 1.5 mites per lash. After 28 days of treatment, Demodex

density decreased to 0.14 ± 0.05 mites per lash, with effects persisting

for more than 90 days and an associated decrease in blepharitis signs.

“At 97% of visits, patients rated the drop as neutral to very

comfortable,” said lead researcher, ophthalmologist Dr Roberto

Gonzalez-Salinas in his virtual Association for Research in Vision and

Ophthalmology (ARVO) presentation. “My colleagues and I are excited

that there is a possible new therapy that targets the underlying cause

of disease for nearly half of all blepharitis patients.”

TP-03 is currently being developed as a multidose, preserved

formulation by Tarsus Pharmaceuticals and phase III trials are

expected to begin later this year.

WWW.EYEONOPTICS.CO.NZ | 23


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

DRY EYE 2020

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

Treat

The epidemiology of dry eye disease

By Dr Michael Wang

DRY EYE DISEASE (DED) as a highly

prevalent and often debilitating condition has

recognised impacts on ocular comfort, visual

function, work productivity, psychological

well-being and quality of life¹ - ³. The 2017

TFOS DEWS II Epidemiology report

highlighted the paucity of studies in the

literature investigating the risk factors and

natural history of DED.

As part of my PhD studies within the

Ocular Surface Laboratory (OSL), we assessed

the systemic risk factors of DED subtypes in a

cohort of 372 community residents, using the

global consensus TFOS DEWS II diagnostic

criteria⁴. Multivariate regression analysis showed

that systemic rheumatological disease and

antidepressant medication use were associated

with increased odds of aqueous tear deficiency.

Independent risk factors for meibomian gland

dysfunction (MGD), the primary cause of

evaporative dry eye disease, included advancing

age, East Asian ethnicity, migraine headaches,

thyroid disease and use of oral contraceptive

therapy. These results highlight the importance

of eye care practitioners routinely enquiring

about systemic health when evaluating patients

with DED. Opportunistic screening and timely

inter-disciplinary referral, arising as a result of

such inquiry, would then enable optimisation

of modifiable systemic risk factors, including

disease activity and medication use, wherever

necessary.

Our associated, second study evaluated

the impacts of ageing on the natural history

of DED in a cohort of 1331 community

residents⁵. In agreement with the trends

reported in previous studies, the results

demonstrated positive associations between

ageing and clinical markers of DED, aqueous

tear deficiency and MGD. On average,

each decade of life was associated with 25%

increased odds of developing dry eye disease.

Of note, clinical signs of MGD emerged earlier

in the natural history of DED progression,

with the optimal prognostic cut-off ages for

meibomian gland dropout, reduced meibum

expressibility and diminished tear film lipid

layer thickness occurring in the third decade

of life, between the ages of 24 to 29 years.

Interestingly, a transient delay was detected

between the appearance of clinical signs of

MGD and other markers of DED, including

tear film instability, hyperosmolarity, lid wiper

Omega fatty acids for DED

By Lesley Springall

FOLLOWING THE SURPRISING

findings from the Dry Eye Assessment and

Management (DREAM) Research Group study

in 2018, which concluded that omega-3 was

no better than olive oil for managing moderate

to severe dry eye disease (DED), a Cochrane

Systematic Review suggests there might still be

a role for the popular fish oil supplement.

Led by Australian TFOS ambassador,

Associate Professor Laura Downie, from

the Department of Optometry and Vision

Sciences at the University of Melbourne, the

Cochrane review set out to assess the effects of

polyunsaturated fatty acid supplements omega-3

and omega-6 on dry eye signs and symptoms.

A search of five national and international

databases and three trial registries highlighted

34 randomised controlled trials, involving

more than 4,300 dry eye patients from 13

countries, where omega-3 and omega-6

supplements were compared with placebo,

artificial tears or no treatment.

“Although much of the evidence was

uncertain, long‐chain omega‐3 supplements

may have little to no benefit, relative to placebo,

on dry eye symptoms, but did improve some

clinical signs,” wrote A/Prof Downie and her

team. The researchers also found there was

some beneficial effect on dry eye symptoms

epitheliopathy and dry eye symptoms, which

predominantly emerged during the fourth

decade of life, between the ages of 33 and 38

years. This brief delay potentially represents

a degree of functional reserve in the ocular

surface, as well as a potential window of

opportunity for preventative intervention

in the younger adult group to attempt to

halt the progression of DED. Finally, and of

importance to clinicians relying on ocular

surface staining in dry eye diagnosis, corneal

and conjunctival staining were among the last

clinical signs of DED to emerge in the natural

history of progression. Such signs of ocular

surface damage typically arose between the

ages of 46 and 52 years and were more likely to

represent moderate-to-severe dry eye disease.

86% MGD has been shown

to affect 86% of

patients with dry eye 1

References

1. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology

Report. Ocul Surf. 2017;15(3):334-365.

2. Uchino M, Schaumberg DA. Dry Eye Disease: Impact on Quality of

Life and Vision. Curr Ophthalmol Rep. 2013;1(2):51-57.

3. Belmonte C, Nichols JJ, Cox SM, et al. TFOS DEWS II Pain and

Sensation Report. Ocul Surf. 2017;15(3):404-437.

4. Wang MTM, Vidal-Rohr M, Muntz A, Diprose WK, Ormonde SE,

Wolffsohn JS, Craig JP. Systemic risk factors of dry eye disease subtypes:

a New Zealand cross-sectional study. Ocul Surf. 2020;18(3):374-380.

5. Wang MTM, Muntz A, Lim J, Kim JS, Lacerda L, Arora A, Craig JP.

Ageing and the natural history of dry eye disease: a prospective registrybased

cross-sectional study. Ocul Surf. 2020 Aug 3; doi: 10.1016/j.

jtos.2020.07.003. Online ahead of print..

Dr Michael Wang is an

neuro-ophthalmology

clinical research fellow

and a PhD student in

the Department of

Ophthalmology at the

University of Auckland.

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

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

Treat

following

the with patients in System LipiFlow the use not CONTRAINDICATIONS:Do Eye. Dry Deficiency Lipid or Eye Dry Evaporative as known also (MGD), Dysfunction Gland Meibomian

including

eyelids, the of conditions cystic chronic with patients adult in therapy pressure and heat localized of application the for intended is System LipiFlow USE:The FOR INDICATIONS

when omega-3 was combined with standard

dry eye treatments, such as artificial tears,

warm compresses and corticosteroid eye drops,

compared to the standard treatments alone.

“Effects on other clinical measures,

including dry eye symptoms and side effects,

could not be clearly determined. It is also

unclear whether other types of supplement

combinations are effective for treating dry

eye. We have low to moderate confidence

in the evidence for all outcomes,” said the

authors, concluding that current evidence

remains uncertain and inconsistent, but that

the review findings did suggest a possible role

for omega‐3 supplements in DED treatment.

“A core outcome set would work toward

improving the consistency of reporting and

the capacity to synthesize evidence.”

For the full review go to, www.cochranelibrary.

com/cdsr/doi/10.1002/14651858.CD011016.

pub2/full

to affect 86% of

shown

been has MGD 86%

patients with dry eye 1

ocular inflammation or history of chronic, recurrent ocular inflammation within prior 3 months (e.g., retinitis, macular inflammation, choroiditis, uveitis, iritis, scleritis, episcleritis, keratitis)

or stye) •Active

hordeolum a including eyelids or sac, lacrimal gland, lacrimal conjunctiva, cornea, the of infection fungal or protozoan, mycobacterial, bacterial, viral, (e.g., infection ocular •Active

compromise corneal integrity (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy)

may that abnormality surface •Ocular ptosis) severe trichiasis, severe lagophthalmos, blepharospasm, edema, tumor, ectropion, entropion, (e.g., function lid affect that abnormalities •Eyelid

result in reduced treatment effectiveness because these conditions may cause ocular symptoms unrelated to cystic meibomian glands and require other medical management. Safety and

with the following conditions may

patients in System LipiFlow the of Use fornices. palpebral small with eyes as such eyes, all fit not may (Disposable) II Activator or Activator PRECAUTIONS:The

inflammation(e.g., blepharochalasis, staphylococcal blepharitis or seborrheic blepharitis). Patients with severe eyelid inflammation should be treated medically prior to device use •Systemic disease

conjunctivitis •Severe (Grade 3 or 4) eyelid

papillary giant or vernal allergic, 2-4) (Grade severe to •Moderate conditions. these with patients in studied been not have device the of effectiveness

erythematosus, Sjögren's syndrome) •Taking medications known to cause dryness (e.g., isotretinoin (Accutane®) and systemic antihistamines) •Esthetic eyelid and eyelash procedures (e.g.,

lupus

systemic syndrome, Riley-Day leukemia, sarcoidosis, granulomatosis, Wegener’s arthritis, rheumatoid deficiency, A vitamin syndrome, Stevens-Johnson eye(e.g., dry cause that conditions

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),

symptoms.

eye dry patient’s the worsen may which plugs, punctal inserted previously loosen may procedure treatment the addition, In tattooing). eyelid extensions, lash blepharoplasty,

Ltd. 507 Mount Wellington Hwy, Mount Wellington, Auckland 1060, New Zealand. Phone: 0800 266 700. PP2018OTH4191

266 111. New Zealand: AMO Australia Pty.

1800 Phone: Australia. 2113, NSW Ryde, North Road, Khartoum 1-5 Ltd, Pty Australia AMO Australia: doi:10.1097/ico.0b013e318225415a. 472-478.

24 | NEW ZEALAND OPTICS SEPTEMBER 2020


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

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

86% MGD has been shown

•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

Treat

Treat

Treat

to affect 86% of

patients with dry eye 1

86% MGD has been shown

to affect 86% of

86%

patients with dry eye MGD has has been shown

1

86%

to to affect 86% of of

MGD patients has with with been dry dry eye shown eye 1 1

to affect 86% of

patients with dry eye

Treat

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

INDICATIONS compromise FOR corneal FOR USE:The integrity USE:The LipiFlow (e.g., LipiFlow prior System System chemical is intended is burn, intended for recurrent the for the corneal application erosion, of localized of localized corneal heat heat epithelial and pressure and pressure defect, therapy Grade therapy in 3 adult corneal in adult patients fluorescein patients with with chronic staining, chronic cystic or cystic map conditions dot conditions fingerprint of the of eyelids, the dystrophy) eyelids, including including

Meibomian PRECAUTIONS:The Gland Gland Dysfunction Activator (MGD), or (MGD), Activator also also known II known (Disposable) as as Evaporative may Dry not Dry Eye fit all or Eye eyes, Lipid or Lipid such Deficiency Deficiency as eyes Dry with Dry Eye. small Eye. palpebral CONTRAINDICATIONS:Do fornices. Use of the not LipiFlow use not the use System LipiFlow the LipiFlow in System patients System in with patients in the patients following with with the conditions following the following may

conditions. result in Use reduced Use of the of treatment device the device in patients effectiveness in patients with with because these these conditions these conditions may may cause may cause injury. cause injury. Safety ocular Safety and symptoms and effectiveness unrelated of the of to device the cystic device have meibomian have not been not glands been studied studied and in require patients in patients other with medical with these these management. conditions. •Ocular Safety •Ocular surgery and surgery

within within effectiveness prior prior 3 months, 3 of months, the including device including have not intraocular, been studied oculo-plastic, in patients corneal corneal with these refractive or refractive conditions. surgery surgery •Moderate procedure procedure to •Ocular severe •Ocular (Grade injury injury within 2-4) within allergic, prior prior 3 vernal months 3 months or Ocular giant Ocular papillary herpes herpes of conjunctivitis eye of or eye eyelid or eyelid •Severe within within prior (Grade prior 3 months 3 or 3 months 4) eyelid

•Active •Active inflammation(e.g., ocular ocular infection infection blepharochalasis, (e.g., (e.g., viral, viral, bacterial, bacterial, staphylococcal mycobacterial, blepharitis protozoan, protozoan, or seborrheic fungal fungal infection blepharitis). infection of the Patients of cornea, the cornea, with severe conjunctiva, eyelid lacrimal inflammation lacrimal gland, gland, lacrimal should lacrimal sac, be treated or sac, eyelids or medically eyelids including including prior a to a device hordeolum use •Systemic stye) or stye) •Active •Active disease

ocular INDICATIONS ocular conditions inflammation that cause FOR or history dry USE:The history eye(e.g., of chronic, LipiFlow of chronic, Stevens-Johnson recurrent System recurrent ocular is intended syndrome, ocular inflammation for vitamin the application within A deficiency, within prior of prior localized 3 months rheumatoid 3 months heat (e.g., and (e.g., arthritis, retinitis, pressure retinitis, Wegener’s macular therapy macular granulomatosis, inflammation, adult patients sarcoidosis, with choroiditis, chronic uveitis, leukemia, uveitis, cystic iritis, conditions iritis, scleritis, Riley-Day scleritis, of syndrome, the episcleritis, eyelids, keratitis) systemic including keratitis) lupus

Eyelid Meibomian •Eyelid erythematosus, abnormalities Gland Sjögren's that Dysfunction that affect syndrome) affect lid function (MGD), lid function •Taking (e.g., also (e.g., known medications entropion, entropion, as Evaporative ectropion, known ectropion, to Dry tumor, cause Eye tumor, dryness edema, Lipid edema, (e.g., Deficiency blepharospasm, isotretinoin Dry (Accutane®) Eye. lagophthalmos, CONTRAINDICATIONS:Do and severe systemic severe trichiasis, antihistamines) trichiasis, severe not severe ptosis) use •Esthetic ptosis) •Ocular LipiFlow •Ocular eyelid surface System and surface eyelash in abnormality patients procedures that with that may the (e.g., may following

conditions. compromise blepharoplasty, corneal Use corneal lash of integrity the extensions, integrity device (e.g., in (e.g., prior patients eyelid prior chemical tattooing). with chemical these burn, In burn, conditions recurrent addition, recurrent the corneal may treatment corneal cause erosion, injury. erosion, procedure corneal Safety corneal epithelial may and epithelial effectiveness loosen defect, previously defect, Grade of the Grade inserted 3 device corneal 3 corneal have punctal not fluorescein plugs, been staining, studied which staining, may or patients map worsen map dot with the dot patient’s these fingerprint conditions. dry dystrophy) eye symptoms. •Ocular surgery

within PRECAUTIONS:The Reference: prior 1. 3 Lemp, months, Activator M. Activator including A., Crews, Activator intraocular, L. Activator A., Bron, II A. II oculo-plastic, (Disposable) J., Foulks, may G. N., corneal may not & fit not Sullivan, all or fit eyes, refractive all B. eyes, such D. (2012). such surgery as eyes as Distribution eyes with procedure with small small of palpebral •Ocular Aqueous-Deficient palpebral injury fornices. fornices. within Use and prior Use of Evaporative the of 3 LipiFlow months the LipiFlow Dry Ocular System Eye System in herpes a in Clinic-Based patients of patients eye with or Patient eyelid with the following Cohort. the within following Cornea, prior conditions 3 conditions months 31(5), may may

result •Active result 472-478. in reduced in ocular reduced doi:10.1097/ico.0b013e318225415a. treatment infection treatment (e.g., effectiveness viral, bacterial, because because these mycobacterial, these Australia: conditions conditions protozoan, AMO may may cause Australia cause or ocular fungal Pty ocular symptoms Ltd, infection symptoms 1-5 Khartoum unrelated of the unrelated cornea, Road, to cystic to conjunctiva, North cystic Ryde, meibomian NSW lacrimal glands 2113, glands gland, Australia. require and lacrimal require Phone: other sac, other or medical 1800 eyelids medical 266 111. including management. New Zealand: a hordeolum Safety Safety AMO and or and Australia stye) •Active Pty.

ocular effectiveness Ltd. 507 inflammation Mount of the of device Wellington the device or have history Hwy, have not been not of Mount chronic, been studied Wellington, studied recurrent patients in Auckland patients ocular with 1060, inflammation with these these New conditions. Zealand. within •Moderate Phone: prior •Moderate 30800 months to severe to 266 severe (e.g., 700. (Grade retinitis, (Grade PP2018OTH4191

2-4) 2-4) allergic, macular allergic, vernal inflammation, vernal or giant or giant papillary choroiditis, papillary uveitis, conjunctivitis iritis, •Severe scleritis, •Severe (Grade episcleritis, (Grade 3 or 34) or keratitis) eyelid 4) eyelid

Eyelid inflammation(e.g., abnormalities blepharochalasis, that affect lid function staphylococcal (e.g., blepharitis entropion, blepharitis or ectropion, seborrheic seborrheic tumor, blepharitis). edema, Patients blepharospasm, Patients with with severe severe lagophthalmos, eyelid eyelid inflammation severe should trichiasis, should be severe treated be treated ptosis) medically medically •Ocular prior prior surface to device to abnormality device use •Systemic use •Systemic that disease may disease

conditions compromise conditions that that cause corneal cause dry integrity eye(e.g., dry eye(e.g., (e.g., Stevens-Johnson prior chemical syndrome, burn, syndrome, recurrent vitamin vitamin corneal A deficiency, A deficiency, erosion, corneal rheumatoid epithelial arthritis, arthritis, defect, Wegener’s Wegener’s Grade 3 corneal granulomatosis, fluorescein sarcoidosis, staining, leukemia, or leukemia, map Riley-Day dot Riley-Day fingerprint syndrome, syndrome, dystrophy) systemic systemic lupus lupus

PRECAUTIONS:The erythematosus, Sjögren's Sjögren's syndrome) Activator syndrome) or •Taking Activator •Taking II medications (Disposable) known known may to cause not to cause fit dryness all dryness eyes, (e.g., such (e.g., as eyes isotretinoin with small (Accutane®) palpebral and systemic and fornices. systemic Use antihistamines) of the LipiFlow •Esthetic •Esthetic System eyelid in eyelid patients and eyelash and with eyelash the following procedures (e.g., conditions (e.g., may

result blepharoplasty, in reduced lash lash treatment extensions, eyelid effectiveness eyelid tattooing). tattooing). because In addition, these In addition, conditions the treatment the treatment may cause procedure procedure ocular may symptoms may loosen loosen previously unrelated previously to inserted cystic inserted meibomian punctal punctal plugs, glands plugs, which and which may require may worsen worsen other the medical patient’s the patient’s management. dry eye dry eye symptoms. Safety and

effectiveness Reference: 1. Lemp, 1. of Lemp, the M. A., device M. Crews, A., have Crews, L. A., not L. Bron, been A., Bron, A. studied J., A. Foulks, J., in Foulks, patients G. N., G. & N., with Sullivan, & these Sullivan, B. conditions. D. B. (2012). D. (2012). •Moderate Distribution Distribution to of severe of Aqueous-Deficient (Grade 2-4) and allergic, and Evaporative vernal Dry giant Eye Dry in Eye papillary a a Clinic-Based conjunctivitis Patient Patient Cohort. •Severe Cohort. Cornea, (Grade Cornea, 31(5), 3 or 31(5), 4) eyelid

472-478. inflammation(e.g., 472-478. doi:10.1097/ico.0b013e318225415a. blepharochalasis, staphylococcal Australia: Australia: blepharitis AMO AMO Australia or seborrheic Australia Pty Ltd, Pty blepharitis). Ltd, 1-5 Khartoum 1-5 Khartoum Patients Road, with Road, North severe North Ryde, eyelid Ryde, NSW inflammation NSW 2113, 2113, Australia. Australia. should Phone: be Phone: treated 1800 1800 266 medically 111. 266 111. New prior New Zealand: to Zealand: device AMO use AMO Australia •Systemic Australia Pty. disease Pty.

Ltd. 507 conditions Ltd. 507 Mount Mount Wellington that Wellington cause dry Hwy, eye(e.g., Hwy, Mount Mount Stevens-Johnson Wellington, Auckland Auckland syndrome, 1060, 1060, New vitamin New Zealand. A Zealand. deficiency, Phone: Phone: 0800 rheumatoid 0800 266 266 700. arthritis, 700. PP2018OTH4191

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. PP2018OTH4191

WWW.EYEONOPTICS.CO.NZ | 25


DRY EYE 2020

Preserved or non-preserved,

that is the question

By Karen Walsh

WITH APOLOGIES TO William Shakespeare

for the title, this was indeed the question

addressed in our recent literature review 1 .

With increasing availability and focus on

preservative-free drops, eye care practitioners

have been left wondering if preserved artificial

tears continue to have a place in the treatment

of dry eye disease (DED).

Any multidose drop must have some

way of maintaining its sterility throughout

its intended length of use. Preservatives are

antimicrobial agents and are used in multidose

drops for this purpose. They must balance an

ability to be efficacious against a wide variety

of pathogens, whilst minimising their toxic

effects on the cells of the ocular surface 2 .

Treatment and symptom alleviation of DED

may require dosing of drops several times a

day, over a period of many years. Any agents

included in dry eye therapies must minimise

their impact on an ocular surface that is

already compromised.

Evidence suggests

that the use of BAKpreserved

drops

should be avoided in

all patients with dry

eye disease

Preservatives to avoid

In all fairness, the concern about the impact

of preservatives on the ocular surface,

especially the potentially compromised

ocular surface of the dry eye patient, is

founded on good evidence. Specifically, the

impact of benzalkonium chloride (BAK)

is widely understood, with its detrimental

effects accumulating over time in a dosedependent

manner 1 . Those adverse changes

are experienced by the user as discomfort

on instillation, burning, stinging and foreign

body sensation, dry eyes, tearing and itchy

eyelids 3 . BAK acts directly on cells including

those of the ocular surface, inducing clinical

signs such as superficial punctate keratitis,

conjunctival hyperemia, blepharitis 3,4 ,

increased osmolarity 5,6 , reduced tear

production 7,8 and reduced tear film breakup

time 7,8 . At the cellular level, BAK reduces

the number of goblet cells and increases

inflammatory responses 9,10 . When the actions

of BAK are viewed in light of the definition of

DED (which recognises the loss of tear film

homeostasis as a central characteristic) 11 , it is

easy to conclude that use of BAK-preserved

drops should be avoided in dry eye disease,

regardless of the severity 1,12 .

Alternative preservatives

Our review examined the ocular surface

compatibility evidence base for a range of

non-BAK alternative preservatives. These

alternatives fall broadly into two categories:

quaternary compounds and oxidising

preservatives.

Polyquaternium-1 (Polyquad, Alcon) is a

hydrophilic, cationic quaternary compound

that is around 27 times larger than BAK and

has a different mode of action 13 . In studies,

although some cell changes have been seen in

vitro 14 , it consistently results in significantly

less disruption to the ocular surface than

BAK-preserved formulations 2,15-17 . Oxidising

preservatives maintain antimicrobial

properties in solution, decomposing to

harmless by-products once applied to the

eye. Examples include stabilised oxychloro

complex (Purite, Allergan; OcuPure, Johnson

& Johnson), and sodium perborate (GenAqua,

Alcon). Previous review papers highlight the

lack of studies on some preservatives in this

group, but in general conclude that they have

significantly less effect on the ocular surface

than BAK 2,18 .

Preservative-free formulations

Preservative-free formulations often come in

single-use vials. Multidose preservative-free

drops are also available, where use is made

of specialised bottles designed to prevent

contamination. Preservative-free drops result

in low levels of ocular surface disruption,

with significant improvements in signs

and symptoms and fewer cellular changes

compared to BAK-preserved drops 3,19-23 .

Depending on study design, preservative-free

drops either show no significant difference

in performance compared to non-BAK

preservatives 24-26 , or cause less disruption than

preserved formulations 17,19,27 .

In practice

Evidence suggests that the use of BAKpreserved

drops should be avoided in all

patients with dry eye disease. The first step

in the TFOS DEWS II staged management

approach suggests the most appropriate

ocular lubricant from the range of non-

BAK preserved options be recommended 12 .

If those measures are inadequate, step two

recommends the use of preservative-free

drops for patients with significant ocular

surface disruption or severe DED 12 . Finally,

given that 86% of patients with DED have

signs of meibomian gland dysfunction 28 ,

the main contributor to evaporative dry eye,

lipid-containing or lipid-stabilising drops can

be particularly helpful. There is currently a

relatively limited choice of preservative-free,

lipid-containing options.

That makes the conclusion to our review,

and the answer to the opening question,

important. Yes, both types of drops can be

considered for most dry eye patients; there is

a place in the treatment of dry eye disease for

both non-BAK preserved and preservativefree

formulations. This evidence-based

conclusion enables the eye care practitioner to

work with individual patients to recommend

the most appropriate formulation for the

subtype of dry eye – aqueous, evaporative or

mixed – that is being treated.

References

1. Walsh K, Jones L. The use of preservatives in dry eye drops. Clin

Ophthalmol. 2019;13:1409-25.

2. Baudouin C, Labbe A, Liang H, et al. Preservatives in eyedrops: the

good, the bad and the ugly. Prog Retin Eye Res 2010;29:312-34.

3. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and

signs with preserved and preservative free glaucoma medication. The

Brit J Ophthalmol 2002;86:418-23.

4. Jaenen N, Baudouin C, Pouliquen P, et al. Ocular symptoms and signs

with preserved and preservative-free glaucoma medications. Eur J

Ophthalmol 2007;17:341-9.

5. Januleviciene I, Derkac I, Grybauskiene L, et al. Effects of preservativefree

tafluprost on tear film osmolarity, tolerability, and intraocular

pressure in previously treated patients with open-angle glaucoma. Clin

Ophthal (Auckland, NZ) 2012;6:103-9.

6. Clouzeau C, Godefroy D, Riancho L, et al. Hyperosmolarity potentiates

toxic effects of benzalkonium chloride on conjunctival epithelial cells in

vitro. Mol Vis 2012;18:851-63.

7. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface

disease in glaucoma patients. J Glaucoma 2008;17:350-5.

8. Yalvac IS, Gedikoglu G, Karagoz Y, et al. Effects of antiglaucoma drugs

on ocular surface. Acta Ophthalmol (Scand) 1995;73:246-8.

9. Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival

changes caused by commonly used glaucoma medications. Cornea

2004;23:490-6.

10. Kahook MY, Noecker R. Quantitative analysis of conjunctival

goblet cells after chronic application of topical drops. Adv Ther

2008;25:743-51.

11. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and

Classification Report. Ocul Surf 2017;15:276-83.

12. Jones L, Downie LE, Korb D, et al. TFOS DEWS II Management and

Therapy Report. The ocular surface 2017;15:575-628.

13. Rolando M, Crider JY, Kahook MY. Ophthalmic preservatives: focus on

polyquaternium-1. Expert Opin Drug Deliv 2011;8:1425-38.

14. Choy CK, Cho P, Boost MV. Cytotoxicity and effects on metabolism of

contact lens care solutions on human corneal epithelium cells. Clin Exp

Optom 2012;95:198-206.

15. Labbe A, Pauly A, Liang H, et al. Comparison of toxicological profiles

26 | NEW ZEALAND OPTICS SEPTEMBER 2020


of benzalkonium chloride and polyquaternium-1:

an experimental study. J Ocul Pharmacol Ther

2006;22:267-78.

16. Brignole-Baudouin F, Riancho L, Liang H, et al.

Comparative in vitro toxicology study of travoprost

polyquad-preserved, travoprost BAK-preserved,

and latanoprost BAK-preserved ophthalmic

solutions on human conjunctival epithelial cells.

Curr Eye Res 2011;36:979-88.

17. Marsovszky L, Resch MD, Visontai Z, et al.

Confocal microscopy of epithelial and langerhans

cells of the cornea in patients using travoprost

drops containing two different preservatives. Pathol

Oncol Res 2014;20:741-6.

18. Gomes JAP, Azar DT, Baudouin C, et al.

TFOS DEWS II iatrogenic report. Ocul Surf

2017;15:511-38.

19. Nasser L, Rozycka M, Gomez Rendon G, et al.

Real-life results of switching from preserved

to preservative-free artificial tears containing

hyaluronate in patients with dry eye disease. Clin

Ophthalmol 2018;12:1519-25.

20. Bron A, Chiambaretta F, Pouliquen P, et al.

[Efficacy and safety of substituting a twice-daily

regimen of timolol with a single daily instillation of

nonpreserved beta-blocker in patients with chronic

glaucoma or ocular hypertension]. J Fr Ophtalmol

2003;26:668-74.

21. Goldberg I, Graham SL, Crowston JG, et

al. Clinical audit examining the impact of

benzalkonium chloride-free anti-glaucoma

medications on patients with symptoms of

ocular surface disease. Clin Exp Ophthalmol

2015;43:214-20.

22. Uusitalo H, Egorov E, Kaarniranta K, et al.

Benefits of switching from latanoprost to

preservative-free tafluprost eye drops: a metaanalysis

of two Phase IIIb clinical trials. Clin

Ophthalmol 2016;10:445-54.

23. Campagna P, Macri A, Rolando M, et al. Chronic

topical eye preservative-free beta-blocker therapy

effect on the ocular surface in glaucomatous

patients. Acta Ophthalmol Scand Suppl 1997:53.

24. Kahook MY, Noecker RJ. Comparison of corneal

and conjunctival changes after dosing of travoprost

preserved with sofZia, latanoprost with 0.02%

benzalkonium chloride, and preservative-free

artificial tears. Cornea 2008;27:339-43.

25. El Hajj Moussa WG, Farhat RG, Nehme JC,

et al. Comparison of Efficacy and Ocular

Surface Disease Index Score between

Bimatoprost, Latanoprost, Travoprost, and

Tafluprost in Glaucoma Patients. J Ophthalmol

2018;2018:1319628.

26. Lee HJ, Jun RM, Cho MS, et al. Comparison of

the ocular surface changes following the use of

two different prostaglandin F2alpha analogues

containing benzalkonium chloride or polyquad in

rabbit eyes. Cutan Ocul Toxicol 2015;34:195-202.

27. Lopez Bernal D, Ubels JL. Quantitative evaluation

of the corneal epithelial barrier: effect of

artificial tears and preservatives. Curr Eye Res

1991;10:645-56.

28. Lemp MA, Crews LA, Bron AJ, et al. Distribution

of aqueous-deficient and evaporative dry eye in a

clinic-based patient cohort: a retrospective study.

Cornea 2012;31:472-8.

Optometrist Karen Walsh is the

professional education team leader

and a clinical scientist at the Centre

for Ocular Research & Education

(CORE), based at the University

of Waterloo, Canada. She has

previously worked in the contact

lens industry and in clinical practice

in the UK and is a fellow of the

International Association of Contact

Lens Educators and the British

Contact Lens Association.

Comparing blood treatments

IN A NEW study, Italian

scientists have found cord

blood to be superior to

adult blood serum eye

drops for treating severe

dry eye disease (DED),

resistant to conventional

therapies.

The multicentre,

double-masked, crossover

clinical study

included 60 patients

with severe dry eye

randomised into

treatment groups: A,

treated with cord blood

serum (CBS) drops; and

B, with peripheral blood

serum drops, eight times

Before PBS treatment (top left); one month after

treatment (top right); two months after the end of

treatment (bottom left); and after one month of CBS

treatment. Credit: bjo.bmj.com/content/104/8/1142

a day for one month. “Corneal staining was more significantly reduced

after the CBS treatment; both visual analogue score and Ocular Surface

Disease Index score reduction was observed in both groups, but group

A reported significantly less grittiness and pain,” wrote researchers.

“Overall, DED signs improved after both CBS and PBS treatments, with

potential advantages of CBS for subjective symptoms and corneal

damage reduction.”

The study was published in the British Journal of Ophthalmology.

by

MILD TO MODERATE DRY EYE

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MODERATE TO SEVERE DRY EYE

BLINK® INTENSIVE TEARS PLUS GEL EYE DROPS

• For moderate-to-severe dry eye symptoms3

• All the advantage of blink® Tears but with a thicker, more viscous lubricating formula3

Ask your Johnson & Johnson Vision Customer Development Manager for more information.

Always read the label. Use as directed.

1. Aragona P.Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye Br J Ophthalol. 2002;86:181-184.

2. Laurent TC. Structure of hyaluronic acid. In: EA balazs (ED.) Chemistry and molecular biology of the intercellular matrix. Academic Press, London; 1970: 703-732

3. Dumbleton, K., Woods, C. and Fonn, D., 2009. An investigation of the efficacy of a novel ocular lubricant. Eye & contact lens, 35(3), pp.149-155.

AMO Australia Pty Ltd, 1-5 Khartoum Road, North Ryde, NSW 2113, Australia. Phone: 1800 736 912 NZ phone: 0800 449 535 Email: Orders@VISAU.JNJ.com

ACUVUE® is a registered trademark of Johnson & Johnson. BLINK® is a registered trademark of Johnson & Johnson Surgical Vision, Inc

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WWW.EYEONOPTICS.CO.NZ | 27


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VitA-POS ®

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• More than 300 individual applications

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NovaTears® Eye Drops (Perfluorohexyloctane 100%, 3mL) are for the lubrication and relief of dry and irritated eyes. Do not use NovaTears® with contact lenses. If using any

other eye medication, allow at least 15 minutes between using the other product and applying NovaTears®. NovaTears® should not be used in children under 18 years.

NovaTears® should not be used while pregnant or breastfeeding. HYLO®-FRESH (Sodium hyaluronate 0.1% w/v, 10mL) and HYLO-FORTE® (Sodium hyaluronate 0.2% w/v, 10mL)

eye drops are General Sales Medicines to improve the lubrication of the eyes, in eyes that are dry, irritated and tired from external factors. AFT Pharmaceuticals, Auckland.

1. Steven, Philipp, et al. “Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease – A Prospective, Multicenter Noninterventional Study.” Journal of Ocular

Pharmacology and Therapeutics 31 (8), 498-503(2015). 2. Steven, Philipp, et al. “Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease Due to Meibomian Gland

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WWW.EYEONOPTICS.CO.NZ | 29


DRY EYE 2020

New point-of-care test for dry eye

By A/Prof Laura Downie

ACCURATE AND EARLY diagnosis of dry eye disease is currently a

clinical challenge, as many current tests are invasive, time-consuming

and inaccurate¹. Dry eye disease affects about one in five adults and

is a common indication for medical eye care in developed countries².

The condition adversely affects the tear film and ocular surface,

potentially leading to eye pain, impaired vision and reduced qualityof-life.

Clinicians have access to a broad range of therapies³ but need to

know which to use and when to use them. It is of critical importance

to determine the main subtype of dry eye (ie. evaporative or aqueousdeficient),

as this informs treatment decisions⁴. However, currently

there is no single method to both diagnose and subtype dry eye disease.

The research programme at the Anterior Eye, Clinical Trials and

Research Translation Unit in the Department of Optometry and

Vision Sciences at the University of Melbourne, integrates laboratory,

clinical and implementation science to support the translation of

discovery research into practice. Over the past three years, one of our

major projects has focused on the development of a new point-ofcare

test for rapid and accurate dry eye diagnosis and subtyping. The

technology is known as ADMiER, acoustically driven microfluidic

extensional rheometry, and involves analysing the viscoelastic

(stretching) properties of a small tear droplet. It is the first application

of microfluidic extensional rheometry for ophthalmic diagnostics. The

ability to both diagnose and subtype dry eye disease using ADMiER, in

a single analytical step, makes the approach a transformative advance

over current tests.

The intended users of this technology are optometrists and

ophthalmologists. Translation of the device into eye care practice

is predicted to benefit eye care clinicians and the healthcare system

by improving practice efficiency through faster, more accurate and

cost-effective patient triaging. For dry eye patients, the diagnostic

and subtyping information provided by the technology will be able to

directly inform treatment, so that dry eye management protocols are

optimised. In the long-term, this has the capacity to drive improvements

in patient health outcomes.

I am currently leading the commercial development of the

technology, in collaboration with Professor Leslie Yeo and Dr Amarin

McDonnell from RMIT University, Melbourne. To date, we have built a

research-grade prototype of the device, secured a strong patent portfolio

and published an initial clinical dataset that demonstrates ADMiER’s

diagnostic utility⁵. Since 2019, our team has presented the technology

at several prestigious scientific meetings and pitched to local potential

investors. Our team was recently awarded a National Health and

Medical Research Council (NHMRC) development grant to support

further development and commercialisation of the technology. This next

stage of development focuses on undertaking a body of research relating

to clinical validation of the device and developing and optimising a

next-generation prototype. We are working towards the ADMiER

product being available on the market within the next five years.

A/Prof Laura Downie

References

1. Downie LE, Keller PR, Vingrys AJ. An evidence-based analysis of Australian optometrists’ dry eye practices.

Optom Vis Sci 2013;90(12):1385-95.

2. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology Report. Ocul Surf 2017;15(3):334-65.

3. Jones L, Downie LE, Korb D, et al. TFOS DEWS II Management and Therapy Report. Ocul Surf 2017;15(3):575-

628.

4. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf

2017;15(3):539-74.

5. McDonnell A, Lee JH, Makrai E, et al. Tear Film Extensional Viscosity Is a Novel Potential Biomarker of Dry Eye

Disease. Ophthalmology 2019.

Associate Professor Laura Downie heads up the Anterior Eye, Clinical Trials and Research

Translation Unit in the Department of Optometry and Vision Sciences at the University of

Melbourne. She is a sought-after international speaker, has published many papers and

served on several national and international expert panels, standards committees and

industry advisory boards, and is an editorial board member on several scientific journals,

including Ophthalmology.

Xiidra pulled

NOVARTIS HAS SHELVED Xiidra in Europe after the European Medicines

Agency (EMA) said its effectiveness in treating dry eye disease (DED) had

not been demonstrated effectively.

Novartis bought the DED prescription eye drop from Takeda

Pharmaceutical last year for US$5.3 billion, including $3.4 billion

upfront and $1.9 billion in milestone payments, three years after the

drop was approved by the US Food and Drug Administration (FDA).

“Although some effect was seen in the reduction of eye dryness,

the improvement was not considered clinically significant,” said the

EMA, noting there was also no long-term data on Xiidra despite DED

being a chronic disease. The clinical

data for Xiidra was further criticised

for only being compared with a

placebo, rather than other eye drop

treatments.

Novartis confirmed it was voluntarily withdrawing its

European marketing application as, “the majority of objections raised

cannot be resolved within the available time frame.” It reserved the

right to make further submissions in the future but confirmed there

were currently no ongoing trials for Xiidra.

30 | NEW ZEALAND OPTICS SEPTEMBER 2020


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WWW.EYEONOPTICS.CO.NZ | 31


DRY EYE 2020

DED and immune-mediated diseases

By Dr Jay Meyer

THE MOST SEVERE forms of

chronic dry eye disease (DED)

are often caused by underlying

immune-mediated diseases.

These can be visually debilitating

in some cases and treatment may

be challenging. Dry eye disease

may result directly or indirectly

from these conditions, some of

which are summarised below. In

general, these conditions often

require treatment with systemic

and/or topical anti-inflammatory

medications to reduce the severity

of dry eye, particularly in the

acute phases of disease.

Sjögren’s syndrome

Sjögren’s syndrome (SS) is

classified using a number of

diagnostic criteria that include

symptoms, signs, histopathologic

features and autoantibodies.

Clinically, SS can be divided

into two subsets: primary SS

includes those without a defined

systemic immune dysfunction

or connective tissue disease,

while secondary SS occurs in

individuals with a connective

tissue disease, most commonly

rheumatoid arthritis or another

auto-immune disease, such as

lupus or scleroderma.

Mechanism of dry eye –

Inflammatory infiltration and

destruction of the lacrimal

glands leads to aqueous tear

deficiency with associated ocular

surface findings, including

punctate epitheliopathy and

even filamentary keratitis in

severe cases (Fig 1). Similar

inflammatory changes may occur

in the salivary glands resulting

in dry mouth and periodontal

disease, although other mucosae

(vaginal, gastric, respiratory) may

also be affected. Viral infections,

including Epstein Barr virus,

hepatitis C and HIV, have been

associated with Sjögren-like

syndromes as well¹.

Treatment considerations –

Standard DED treatments can

be employed but more advanced

treatments, such as punctal

occlusion or serum tears, may

be required. In patients with

active systemic autoimmune

inflammation, allogeneic serum

tears (from related or unrelated

donors) may be preferred due to a

theoretical concern of increasing

ocular surface inflammation if

using autologous serum (from the

patient)². Given the underlying

immune-mediated process, antiinflammatory

treatment, such as

chronic topical cyclosporine or

topical corticosteroids in pulsed

doses, may be considered or be

necessary.

Graft-versus-host disease

Graft-versus-host disease

(GVHD) is a complication

following bone marrow

transplantation, most commonly

performed for haematopoietic

malignancies. GVHD results from

the grafted cells attacking the

recipient and may affect multiple

tissues, including the eyes, and it

can be acute or chronic.

Mechanism of dry eye – Ocular

surface damage can result from

conjunctival inflammation and

Fig 1. Diffuse punctate corneal fluorescein staining and limbal filament in a patient with

Sjögren’s syndrome

Fig 2. Subepithelial conjunctival fibrosis and foreshortening of the inferior fornix due to

chronic GVHD

lacrimal gland infiltration by

lymphocytes. Most commonly,

inflammation causes ocular

surface dryness due to aqueous

tear deficiency, although

more severe cases can result

in subepithelial fibrosis of the

conjunctiva (Fig 2), cicatricial

lagophthalmos and even

limbal stem cell deficiency and

secondary corneal scarring.

Treatment – These individuals

frequently have non-ocular

GVHD for which they

receive potent systemic

immunosuppression treatment.

In addition, chronic topical

anti-inflammatory treatment

with topical cyclosporine and/

or corticosteroids may be

required. Amniotic membrane

transplantation can be considered

for severe cases (see p42).

Thyroid Eye Disease

Thyroid eye disease (TED)

results from immune-mediated

inflammation of the orbit and

develops in a large proportion of

individuals with Graves’ disease.

Mechanism of dry eye – Most

patients with TED have dry

eye disease due to various

mechanisms. Evaporative dry

eye and corneal exposure may

result from the combination of

proptosis and lid retraction and

subsequent incomplete blinking

and nocturnal lagophthalmos.

In addition, antibody-induced

inflammation and infiltration

may lead to lacrimal gland

enlargement and abnormalities in

the composition of tears³.

Treatment considerations –

Ocular lubrication with artificial

tears and ointments are the

mainstay of treatment. Patients

with severe proptosis may

require orbital decompression for

diplopia, which can also benefit

the DED by restoring lid function.

Systemic immunosuppression

with corticosteroids or other

medication may be required

for severe TED with active

inflammation.

Coeliac Disease

Coeliac disease involves an

immune response to dietary

gluten that frequently manifests

as diarrhoea and weight loss.

Mechanism of dry eye –

Malabsorption of nutrients may

lead to vitamin A deficiency

xerosis due to associated loss

of mucus production by the

goblet cells, and mild vitamin A

deficiency can result in ocular

surface dryness. More advanced

vitamin A deficiency can lead

to Bitot’s spots, or even corneal

ulceration (keratomalacia)

although deficiency this severe

would rarely be due to coeliac

disease. Nyctalopia, or night

blindness, may be another

symptom of hypovitaminosis

A. Other non-immune causes

of vitamin A deficiency include

dietary insufficiency and bariatric

surgery leading to malabsorption.

Treatment considerations –

Treatment involves systemic

replacement of any vitamin A

32 | NEW ZEALAND OPTICS SEPTEMBER 2020


deficiency by a physician. Topical

vitamin A ointment can also be

administered as an adjunctive

treatment.

Immune-mediated disorders

of skin and mucous

membranes

Oculocutaneous immunemediated

diseases include

cicatricial pemphigoid,

Stevens-Johnson

syndrome, toxic epidermal

necrolysis, GVHD, atopic

blepharokeratoconjunctivitis

and rosacea, among others.

These conditions can cause

inflammation that leads to

destruction of conjunctival

goblet cells and, in some cases,

obstruction of lacrimal gland

ductules. The subsequent aqueous

and mucous tear deficiency may

lead to keratinisation of the

ocular surface as well as corneal

vascularisation, scarring and

ulceration.

Treatment considerations

– The majority of these

conditions require systemic

immunosuppression to control

the inflammation and this

is usually prescribed by an

immunologist. Topical antiinflammatory

treatment is

also frequently necessary

and amniotic membrane

transplantation may be beneficial.

Tacrolimus ointment applied

to the eyelids can be a useful

alternative to corticosteroids for

patients with blepharitis due to

atopy or rosacea.

References

1. Ramos-Casals M, Brito-Zerón P, Font J. Lessons

from diseases mimicking Sjögren’s syndrome. Clin

Rev Allergy Immunol 2007;32(3):275-283.

2. Chiang CC, Lin JM, Chen WL, Tsai YY. Allogeneic

serum eye drops for the treatment of severe dry eye

in patients with chronic graft-versus-host disease.

Cornea. 2007;26(7):861-863.

3. Khalil HA, de Keizer RJ, Kijlstra A. Analysis of

tear proteins in Graves’ ophthalmopathy by

high performance liquid chromatography. Am J

Ophthalmol 1988;106(2):186-190.

Dr Jay Meyer is a

subspecialist in cornea/

external diseases and

glaucoma. He is a consultant

ophthalmologist at Eye

Institute and the Auckland

District Health Board, and

a senior lecturer at the

University of Auckland.

Ezcema treatment exacerbates DED

EUROPEAN RESEARCHERS

HAVE recommended patients

with eyelid eczema be referred

to an ophthalmologist before

being prescribed dupilumab

after finding the treatment

likely caused or aggravated

dry eye disease (DED) in a

French study.

The study, published in the Journal of European

Academy of Dermatology and Venereology, included

46 patients, suffering from atopic dermatitis with

a median age of 41.1 years who were recruited

from a French university hospital and treated with

DRY EYE

RELIEF

FROM

THE INSIDE

• Works systemically from the inside

• Improves tear film quality

• Increases tear production

• Excellent adjunct to drops

P Concentrated Fish Oil

P Flax Seed Oil

P Borage Oil

Research has shown that the combination of Omega-3 containing DHA and EPA plus Alpha

Linolenic Acid and plant-based Omega-6 fatty acids like Gamma-Linolenic Acid can help improve

the oily lipid layer of the tear, reduce inflammation resulting in improved tear production and

tear film break-up time. Lacritec is specially formulated based from this research and because it is

systemic, provides more continuous relief from dry eye discomfort and may replace the need for

eye drops for many patients.

Available at selected Optometrists or FreeCall 0800 622 883.

Always read the label. Use only as directed. If symptoms persist see a healthcare professional.

Supplementary to and not a replacement for a balanced diet.

Contact Stiltec Global on 0800 622 883

or info@stiltec.com.au

dupilumab between April

2017 and October 2019.

“The majority developed

or reported aggravated dry

eye disease, with superficial

punctate keratitis,” reported

researchers, adding that

six patients developed

conjunctivitis and two

discontinued dupilumab because of the severity of

their ocular adverse events (OAEs).

“Further multicentric and translational studies are

warranted to better explain OAEs pathophysiology,”

they concluded.

www.lacritec.co.nz

WWW.EYEONOPTICS.CO.NZ | 33


EYE ON OPHTHALMOLOGY

Castor oil for blepharitis

By Dr Alex Müntz and A/Prof Jennifer Craig

BLEPHARITIS IS ONE of the most

common ophthalmic conditions,

characterised by chronic inflammation

of the eyelid tissues and affecting the

eyelashes, meibomian glands and ocular

surface. Causative and contributing

mechanisms are diverse and include

bacterial over-colonisation, a destabilised

tear film, infestation with Demodex,

atopy and seborrhoea and associated

over-activation of host immune and

inflammatory responses. However,

these factors are only moderately well

understood. Patients present with lid

margin itching, burning, flaking, crusting,

redness, photophobia and epiphora. Overall,

blepharitis is often associated with a reduction

in quality of life 1,2 .

Acute blepharitis flare ups are commonly

treated with topical antibiotics and antiinflammatory

agents, while regular eyelid

hygiene and heat-based therapy are considered

indispensable for ongoing symptomatic

control. However, these strategies tend to

be either palliative or limited by microbial

resistance and unwanted side effects.

Additionally, long-term patient adherence

to home-based therapy is notoriously

problematic. Innovative interventions that

target the underlying causes of blepharitis are

thus highly sought after 3–5 .

Ricinus communis: Credit H Zell

Fig 1. Rollerball application of castor oil at the lower and upper lid margin

Castor oil properties and use

Castor oil is a natural derivative of the

Ricinus communis plant, an ancient ethnopharmaceutical

with anti-inflammatory,

anti-nociceptive, antioxidant, antimicrobial

and insecticidal properties 6–10 . Extracted

or pressed from the plant beans, the main

component in castor oil is ricinoleic acid,

along with various other oils, fatty acids,

vitamins and trace elements. A natural

triglyceride, this hydroxylated unsaturated

fatty acid possesses surfactant, cleansing,

skin conditioning and emulsion-stabilising

properties 11 . It is used industrially, as well as

for medical purposes in wound dressings, as a

solvent for intramuscular injections and as a

drug delivery vehicle. Ophthalmic applications

involve castor oil as an emollient or vehicle in

eye drop formulations, mostly in conjunction

with cyclosporine. In this context, castor oil

was serendipitously discovered to address tear

film lipid insufficiency and instability and

has been proposed as a management option

for dry eye disease and meibomian gland

dysfunction 12–16 .

A promising alternative to conventional eye

drops is the external application of agents such

as liposomal sprays or manuka honey*. These

formulations have demonstrated benefits in

managing ocular surface disease, owing to the

presumed migration of the active ingredient

across the lid margin into the tear film

and onto the ocular surface 17,18 . In anterior

blepharitis, the chronic inflammation of lash

follicles is associated with eyelash thinning,

whitening, madarosis and trichiasis. Lid

hygiene has a positive impact by decreasing

inflammation 19 . It was therefore hypothesised

that the periocular application of castor oil

might be advantageous. Its anti-inflammatory

nature may directly target the downstream,

chronic, low-grade inflammation associated

with blepharitis, while its purported ability to

address tear film lipid deficiency secondary

to meibomian gland dysfunction (MGD),

through lipid supplementation, may further

contribute to management of the condition.

The limited therapeutic options for

blepharitis, coupled with growing interest

in natural remedies, provided a nexus of

opportunity for researchers in the Ocular

Surface Laboratory (OSL) and collaborators

to investigate the potential efficacy of castor

oil for the management of blepharitis in

a randomised controlled trial, recently

published in The Ocular Surface journal 20 .

Study design

Twenty-six participants (53% female, mean

age: 38 ± 21 years, between 20 and 79 years)

with one or more clinical signs of anterior

blepharitis and MGD were recruited into the

randomised controlled trial. Participants were

randomly assigned to apply unpreserved,

100% cold-pressed castor oil (Lotus Garden

Botanicals) to either the left or the right

eye, twice daily, for a period of four weeks.

The fellow eye received no intervention as a

control.

Instructions on the application of a thin

film of castor oil on the eyelid skin using a

rollerball applicator were provided (Fig 1).

Castor oil was applied twice a day, 30 minutes

before eye cosmetic wear, if worn, in the

morning and following make-up removal in

the evening. Participants were asked not to use

castor oil on the day of the one-month followup

visit to avoid unmasking the investigator.

Bottles were weighed at baseline and at followup

as a measure of patient compliance.

Clinical measurements followed the

TFOS DEWS II diagnostic consensus

recommendations and were performed at

baseline and on day 28. Symptoms were

assessed using the Ocular Surface Disease

Index (OSDI) and the five-item Dry Eye

Questionnaire (DEQ-5). Bulbar conjunctival

34 | NEW ZEALAND OPTICS SEPTEMBER 2020


Professors

Charles McGhee

& Dipika Patel,

series editors

hyperaemia, tear meniscus height, noninvasive

tear film breakup time and tear

film lipid layer grade were assessed using

the Keratograph 5M (Oculus). The tear film

lipid layer thickness was evaluated with

the Lipiview ocular surface interferometer

(Johnson & Johnson) and tear film osmolarity

was measured with a clinical osmometer

(Tearlab).

A slit lamp biomicroscopy examination

was conducted to assess lid margin and

eyelash abnormalities, including lid margin

thickening, rounding, notching, foaming,

telangiectasia, staphylococcal and seborrhoeic

lash crusting, Demodex lash cylindrical

dandruff, madarosis, trichiasis and meibomian

gland capping. Corneal, conjunctival and lid

margin staining was assessed using sodium

fluorescein and lissamine green clinical

dyes. Meibum quality and meibomian

gland expressibility of the inferior eyelid

were assessed using the Meibomian Gland

Evaluator (Johnson & Johnson). Infrared

meibography images were recorded from

everted eyelids using the Keratograph 5M,

while Demodex presence was determined by

lash epilation and light microscopic analysis.

Study results

After four weeks of castor oil use, significant

improvements in symptoms were reflected

in improved OSDI (19.8 ± 13.7 versus 14.0

± 12.4) and DEQ-5 (9.4 ± 3.1 versus 8.2 ±

3.3) scores (p


DRY EYE 2020

Continued from p35

Acknowledgements

The authors acknowledge current and previous

OSL members who contributed to this

research, including Marna Claassen, Lauren

Curd and Alice Jackson who undertook this

research as a BOptom honours project, Dr

Michael Wang and Grant Watters, as well as all

study participants who took part. The authors

are also grateful to Dr Emma Sandford whose

passion for natural ophthalmic healthcare

served as the inspiration for this project.

References

1. McCulley JP, Shine WE. Eyelid disorders: the meibomian gland,

blepharitis, and contact lenses. Eye Contact Lens 2003; 29: S93-95.

2. Buchholz P, Steeds CS, Stern LS, et al. Utility assessment to measure the

impact of dry eye disease. Ocul Surf 2006; 4: 155–161.

3. Lindsley K, Matsumura S, Hatef E, et al. Interventions for chronic

blepharitis. Cochrane database Syst Rev 2012; 16: 1–117.

4. Pflugfelder SC, Karpecki PM, Perez VL. Treatment of blepharitis: recent

clinical trials. Ocul Surf 2014; 12: 273–284.

5. Duncan K, Jeng BH. Medical management of blepharitis. Curr Opin

Ophthalmol 2015; 26: 289–294.

6. Marwat SK, Fazal-Ur-rehman. Ricinus communis: Ethnomedicinal uses

and pharmacological activities. Pak J Pharm Sci 2017; 30: 1815–1827.

7. Momoh A., Oladunmoye MK, Adebolu TT. Evaluation of the

antimicrobial and phytochemical properties of oil from castor seeds

( Ricinus communis Linn). Bull Environ Pharmacol Life Sci 2012; 1:

21–27.

8. Vieira C, Evangelista S, Cirillo R, et al. Effect of ricinoleic acid in acute

and subchronic experimental models of inflammation. Mediators

Inflamm 2000; 9: 223–228.

9. Pabiś S, Kula J. Synthesis and bioactivity of (R)-ricinoleic acid derivatives:

A review. Curr Med Chem 2016; 23: 4037–4056.

10. Jena J, Gupta AK. Ricinus communis linn: A phytopharmacological

review. Int J Pharm Pharm Sci 2012; 4: 25–29.

11. CIR expert panel. Final report on the safety assessment of Ricinus

communis (castor) seed oil, hydrogenated castor oil, glyceryl ricinoleate,

glyceryl ricinoleate SE, ricinoleic acid, potassium ricinoleate, sodium

ricinoleate, zinc ricinoleate, cetyl ricinoleate, ethyl ric. Int J Toxicol 2006;

26: 31–77.

12. Di Pascuale MA, Goto E, Tseng SCG. Sequential changes of lipid tear

film after the instillation of a single drop of a new emulsion eye drop in

dry eye patients. Ophthalmology 2004; 111: 783–791.

13. Khanal S, Tomlinson A, Pearce EI, et al. Effect of an oil-in-water

emulsion on the tear physiology of patients with mild to moderate dry

eye. Cornea 2007; 26: 175–181.

14. Goto E, Shimazaki J, Monden Y, et al. Low-concentration homogenized

castor oil eye drops for noninflamed obstructive meibomian gland

dysfunction. Ophthalmology 2002; 109: 2030–2035.

15. Maïssa C, Guillon M, Simmons P, et al. Effect of castor oil emulsion

eyedrops on tear film composition and stability. Contact Lens Anterior

Eye 2010; 33: 76–82.

16. Scaffidi RC, Korb DR. Comparison of the efficacy of two lipid emulsion

eyedrops in increasing tear film lipid layer thickness. Eye Contact Lens

2007; 33: 38–44.

17. Craig JP, Wang MTM, Ganesalingam K, et al. 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: 1–9.

18. Craig JP, Purslow C, Murphy PJ, et al. Effect of a liposomal spray on the

pre-ocular tear film. Contact Lens Anterior Eye 2010; 33: 83–87.

19. Sung J, Wang MTM, Lee SH, et al. Randomized double-masked trial of

eyelid cleansing treatments for blepharitis. Ocul Surf 2018; 16: 77–83.

20. Muntz A, Sandford E, Claassen M, et al. Randomized trial of topical

periocular castor oil treatment for blepharitis. Ocul Surf. Epub ahead of

print 2020. DOI: 10.1016/j.jtos.2020.05.007.

*https://eyeonoptics.co.nz/articles/archive/

manuka-honey-cream-for-blepharitis/

Dr Alex Müntz is an optometrist

and a post-doctoral research

fellow in the OSL at the

University of Auckland and was

previously a clinical research

scientist with the Centre for

Ocular Research & Education at

the University of Waterloo.

Associate Professor Jennifer

Craig is head of the Ocular

Surface Laboratory and a

therapeutically qualified

academic optometrist in

the University of Auckland’s

Department of Ophthalmology.

Dry eye technology:

improving outcomes

By Ryan Mahmoud

MY PRACTICE FOCUSES

on specialty eye care and,

much to my surprise, dry

eye continues to be one of

our main drawcards and

is continuing to grow. I

believe a lot of the success

we have experienced with

dry eye has been due to the

implementation of the latest

dry eye technology. From

a diagnostic perspective,

dedicated systems provide

a level of detail that allows

for more precise diagnosis

and better monitoring of

treatment outcomes; while

from a treatment perspective,

advanced technology allows

for more intense therapy

that offers shorter treatment

times with improved patient

compliance.

Treating dry eye doesn’t

happen overnight. It is more

of a rehabilitation process

than expecting results from

a quick, one-off treatment.

It also requires patient

buy-in and trust in your

diagnosis and treatment

plan, and this trust needs

to endure for months as the

treatment progresses, often with only subtle

improvements in symptoms in the initial

stages. Key to keeping that trust intact is the

use of technology.

Meibography: a game changer

One of the key developments in dry eye

diagnostic technology has been the ability to

image the meibomian glands. Meibography

allows you to visualise how blocked

(damaged) the glands are and judge how

quickly you might expect your treatment to

work. More importantly though, it allows

the patient to see their meibomian gland

dysfunction (MGD) for themselves. This has

a powerful effect on patients and sets the

foundation for good treatment compliance

going forward.

Imaging and encouragement

While imaging is a powerful tool, so too

is encouragement. Combine the two

together and you have a recipe for good

compliance. Even in the absence of symptom

improvement, when patients see their clinical

signs improving, confirming their hard work

is paying off, it encourages them to persist

Ryan Mahmoud with a dry eye patient

Ryan Mahmoud treating a dry eye patient with Rexon-Eye

with their treatments. A dry eye topographer,

that allows you to demonstrate improvements

in lipid layer thickness and non-invasive tear

breakup time, is key to reassuring patients

that their symptoms are likely to improve

soon and encourage them to follow through

with your treatment recommendations.

A dry eye topographer also allows you to

accurately monitor treatment progression

and share the results. Some treatments

become effective over an extended period,

but without technology to confirm subtle

changes in the tear film or ocular surface,

it can be difficult to convince a patient to

continue with current treatments without

obvious symptomatic improvement, and this

could force you to alter a treatment strategy

that might have been very effective if given

sufficient time.

A patient of mine who went from

depending on autologous serum drops to

requiring no drops at all, recently told me our

follow-up sessions were key to encouraging

her to continue with treatment. Seeing

improvements in measurements gives patients

reassurance they are not wasting their time.

36 | NEW ZEALAND OPTICS SEPTEMBER 2020


Technology for treatment

Warm compresses used properly are very effective and I prescribe

them routinely. However, for many of my more severe patients,

compresses are just not enough to get their dry eye under control. At

my practice, I have an extensive range of dry eye treatment options

including Lipiflow, E>Eye and, most recently, I’ve introduced the

Rexon-Eye.

Lipiflow

Lipiflow is a great treatment for MGD. It involves a single,

12-minute session of thermal pulsation on the eyelids and symptom

improvement is typically noticed after about four weeks. Longterm

studies show improvements in signs for up to three years

and symptoms for up to two years. I have found that one year is

the average, but patients can extend this further if they continue

maintenance therapy at home. Longer-term follow-up studies are one

of the key advantages that Lipiflow has over other devices as I can

confidently give patients an estimate of how long they can expect the

effect of their treatment to last. Also, the fact that it requires only one

session, makes it a good option for patients that live far away and find

it difficult to come in for multiple treatment sessions. I have treated

several patients that live outside Auckland and even patients who

live overseas. But for patients with very severe gland loss, I tend to go

with one of the other treatment options, as I find that the response to

Lipiflow is less effective in these patients.

E>Eye IPL

The E>Eye intense regulated pulsed light or IPL course of treatment

involves four IPL sessions spread over a 70-day period. I also add

manual expression of the lids after each session. I have found a

noticeable improvement with this treatment in reducing lid margin

inflammation, therefore I tend to favour this treatment when lid

margin inflammation is very visible. I also tend to favour it when

meibography shows extensive gland loss, since it is postulated that

IPL doesn’t just work on the glands, but also has anti-inflammatory

and anti-bacterial effects.

Rexon-Eye: finally, a treatment for aqueous deficiency

Earlier this year, we became the first practice in New Zealand to

acquire a Rexon-Eye device*. I was attracted to the device as early

studies showed it resulted in improvements in meibomian gland

expression, corneal surface staining and, most impressively, tear

secretion. For me, this was the missing tool in our arsenal as we

didn’t have a convincing treatment for aqueous deficient dry eye.

The treatment uses electrical currents at a therapeutic frequency,

termed ‘quantum magnetic resonance’ by the manufacturer, which

are applied to the eyelids via goggles. The treatment consists of

four, 20-minute sessions over four weeks. Having had the treatment

myself, I would describe it as comparable to having a warm compress

applied to the eyes.

My experience with patients so far has been that it does indeed

appear to increase tear secretion and lead to improvements in

meibomian gland function. One of its key advantages, is that I find

it improves symptoms within one day of the first treatment session.

I can therefore test it out on patients before making a decision about

proceeding with the remaining three sessions. I have been using

it for patients with signs of aqueous deficiency and as a follow-up

treatment to Lipiflow when patients want to experience faster results.

In summary, dry eye technology has allowed me to diagnose dry

eye better and treat it more effectively. I have been able to achieve

favourable results for my patients and offer them relief from their

pain and discomfort and, in the end, that’s what this is all about.

* https://eyeonoptics.co.nz/articles/archive/new-dry-eye-deviceunveiled-in-nz/

Ryan Mahmoud is a therapeutically trained optometrist and owner of NVision

Eyecare in Auckland, New Zealand. NVision offers speciality services in myopia

control, RGP contact lens fitting and dry eye.

WWW.EYEONOPTICS.CO.NZ | 37


Visit eyeonoptics.co.nz or eyeonoptics.com.au

for the latest news, features, research updates,

industry comment, job adverts and more.

38 | NEW ZEALAND OPTICS SEPTEMBER 2020


DRY EYE 2020

DED and the

Dunedin Study

By Dr Michael Wang, Dr Graham Wilson and A/Prof Jennifer Craig

THE DUNEDIN MULTIDISCIPLINARY Health and Development

Study (Dunedin Study) is a large longitudinal study investigating human

health, development, ageing and behaviour, which tracks a populationrepresentative

birth cohort born between 1972 and 1973 in Dunedin,

New Zealand.

In the current phase, participants were assessed at the age of 45

and, for the first time, underwent a comprehensive dry eye evaluation.

The reports from the recent global consensus Tear Film and Ocular

Surface Society’s second dry eye workshop (TFOS DEWS II) noted

the significant shortage of epidemiological data from the southern

hemisphere on the prevalence and risk factors of dry eye disease, thus

the Dunedin Study is ideally placed to address some of these gaps in the

current dry eye literature.

The recently published results from the dry eye arm of the Dunedin

Study showed that the prevalence of dry eye disease was 9% in these

45-year-old New Zealanders 1 . The prevalence rate was comparable to

those reported by the meta-analysis conducted by the TFOS DEWS II

epidemiology subcommittee, which highlighted that, globally, dry eye

disease was present in between 8 and 15% of 40 to 49-year-old adults 2 .

Among those with dry eye disease in the Dunedin Study cohort, a

significant majority (82%) had meibomian gland dysfunction, while

just over one quarter (28%) had aqueous tear deficiency, which is

also consistent with previous studies that report meibomian gland

dysfunction to be the predominant contributor to dry eye disease

worldwide 3,4 . Interestingly, a considerable proportion (37%) of the

study cohort exhibited asymptomatic ocular surface disease which

may, potentially, represent an opportunity for the introduction of

preventative public health strategies. In line with the trends reported

by earlier studies¹, female participants in the Dunedin Study cohort

were more likely to be afflicted with dry eye disease, meibomian gland

dysfunction and asymptomatic ocular surface disease than their male

counterparts.

Future planned analysis of the Dunedin Study will involve

examination of the potential associations and interactions between

mental health, systemic medical conditions and dry eye disease to

facilitate further characterisation of modifiable and non-modifiable

risk factors for the development of dry eye disease. The investigation

of the relationship between human health, development, ageing and

dry eye disease will also enable further exploration of whether ocular

surface and tear film parameters might serve as biomarkers for the

ageing process.

Acknowledgements

We are indebted to the study team and to the study members for their

contribution to this research and are grateful to the Rapanui Trust

(Gisborne) for supporting the purchase of the Oculus Keratograph 5M.

References

1. Craig JP, Wang MTM, Ambler A, Cheyne K, Wilson GA. Characterising the ocular surface and tear film in

a population-based birth cohort of 45-year old New Zealand men and women. Ocul Surf 2020 Aug 13; doi:

10.1016/j.jtos.2020.08.005. Online ahead of print.

2. Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, et al. TFOS DEWS II Epidemiology Report.

Ocul Surf. 2017;15:334-65.

3. Rabensteiner DF, Aminfar H, Boldin I, Schwantzer G, Horwath-Winter J. The prevalence of meibomian gland

dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population. Acta Ophthalmol.

2018;96:e707-e11.

4. Rege A, Kulkarni V, Puthran N, Khandgave T. A clinical study of subtype-based prevalence of dry eye. J Clin

Diagn Res. 2013;7:2207-10.

Dr Michael Wang is currently a clinical research fellow and PhD student at the

University of Auckland, Dr Graham Wilson is a Gisborne-based ophthalmologist and

principal investigator for all eye-related matters on the Dunedin Study and A/Prof

Jennifer Craig is an associate investigator on the Dunedin study, based at the Ocular

Surface Laboratory at the University of Auckland.

DED market grows

THE MARKET FOR dry eye disease drugs is expected to continue to

grow significantly regardless of the Covid-19 pandemic.

Driven by a more well-informed eye care professional and public

market, better diagnostic tools and treatments, the global dry eye

drugs market is expected to grow by 11.5% from US$6.97 billion

to US$10.78 billion between 2020 and 2025, according to market

research company 360 Market Updates.

WWW.EYEONOPTICS.CO.NZ | 39


DRY EYE 2020

When should you check for dry eye?

By Dr Scott Schachter

SHOULD WE LOOK for dry eye on every patient? I get this question

with some frequency. I admit I find it perplexing. I am reminded of a

practitioner asking me several years ago if I did biomicroscopy on every

patient. Well, of course! Do I look for dry eye disease on every patient?

The answer is a resounding YES! Allow me to explain why.

There’s a lot of it

It is well-established that dry eye disease (DED) is prevalent¹. We often

hear that it is ‘multifactorial’. What does that mean precisely? It means

that many roads lead to DED and that’s why there are so many dry eye

sufferers. Some common culprits are age, sex, medications, device use,

topical preservatives, nutrition, environment, migraine, ophthalmic

surgery, autoimmune disease and meibomian gland dysfunction. Does

this sound like your patient base?

While postmenopausal women are highest on the suspect list for dry

eye, device use and medications are two of the more common causes of

symptoms in younger people. A 2016 study looked at 630 subjects, of

which 60 had both signs and symptoms of DED. Thirty of these stopped

all smartphone use for four weeks and their rate of dry eye went from

100% to 0%. While that statistic is undoubtedly impressive, even more

shocking is the age range of the subjects: seven to 12 years old²!

When reviewing patient medications meanwhile, antidepressants

and antipsychotics have the highest odds of causing dry eye disease³. A

2014 Australian paper found a significant increase in the prescribing of

antidepressants, antipsychotic and ADHD medications between 2009

and 2012. For children aged 10-14, antidepressant and antipsychotic

dispensing went up 36% and 49% respectively. For patients aged 20-24

years old, ADHD medication was prescribed 71% more⁴.

It affects vision

My personal introduction to the visual effects of DED was during my

own LASIK consultation, where it was revealed that I had higher-order

aberrations. As a low spherical myope, that didn’t make sense. The

surgeon treated me for dry eye and within two weeks the aberrations

were gone. This was an epiphany – the tear film affects vision⁵! This is

something I had overlooked. I started thinking of dry eye as a ‘vision

disease’ and, as a ‘vision doctor’, I decided to look for dry eye on every

patient.

It affects quality of life

Once viewed simply as a nuisance, dry eye is now recognised as a

Dr Scott Schachter treating a dry eye patient

disease. Patients with dry eye may have difficulty reading, driving,

watching television and other activities of daily living⁶. Using a

30-minute, 7200-word passage, Akpek et al found that dry eye patients

with corneal damage read nearly 28 words per minute slower compared

with ‘normals’, while their reading speed correlated with the amount of

corneal staining⁷. As we all aim to reduce dry eye symptoms, keep in

mind that a clear cornea is also a worthwhile goal.

There are many treatment options

Before 2003, artificial tears and warm compresses were about the

only options we could offer dry eye-suffering patients. Fast forward

to 2020 and, in the US at least, we have three prescription dry eye

medications, three in-office meibomian gland expression devices,

amniotic membranes, autologous serum eye drops and numerous other

choices; recently, a topical medication for neurotrophic keratitis was

released. And the therapeutic pipeline is strong: look soon for a topical

prescription eye drop for blepharitis, a keratolytic for meibomian gland

dysfunction and more preservative-free eye drop delivery systems.

Treating DED helps both patient and practice

As a result of my ‘vision disease’ epiphany, I implemented an algorithm

to screen, diagnose and treat dry eye. Within six months, therapeutic

practice visits tripled, while revenue per patient remained the same.

I am often introduced as a practitioner who is ‘aggressively’

diagnosing and treating ocular surface disease. Rather, I am actually

‘appropriately’ doing so. I simply follow expert recommendations, which

I had been oblivious to previously. My algorithm was initially based on

the TFOS Dry Eye Workshop of 2007 and has since evolved with the

2017 TFOS DEWS II update. I strongly recommend TFOS DEWS II as

a starting point for diagnosing and treating dry eye; it is an evidence-

40 | NEW ZEALAND OPTICS SEPTEMBER 2020


ased consensus with a stepwise treatment protocol.

While my approach is backed by science, it is also ‘streamlined’ to

be efficient and straightforward, to ensure it is sustainable in practice.

Weekly, patients thank us for taking the extra time to address their

complaints which remained unaddressed by other practitioners. As a

result, we get many patient referrals and practitioner consults as well.

Becoming a local ‘dry eye clinic’ can be a significant practice builder.

In conclusion

So, should you look for dry eye on every patient? Yes, yes, yes! As

vision care providers, vision begins at the tear film. With such a high

prevalence, as well as impact on vision and quality of life, you owe it to

your patients to take a look and, if treating dry eye patients is not for

you then send them to someone who does. Your patients deserve it!

References

1. Nelson JD, Craig JP, Akpek EK, et al. TFOS DEWS II Introduction. Ocul Surf. 2017;15(3):269-275.

2. Moon, J.H., Kim, K.W. & Moon, N.J. Smartphone use is a risk factor for pediatric dry eye disease according to

region and age: a case control study. BMC Ophthalmol 16 (1), 188.

3. Gomes JAP, Azar DT, Baudouin C, et al. TFOS DEWS II Iatrogenic Report. Ocul Surf. 2017;15(3):511-538.

4. Karanges EA, Stephenson CP, McGregor IS. Longitudinal trends in the dispensing of psychotropic medications

in Australia from 2009-2012: focus on children, adolescents and prescriber specialty. Aust N Z J Psychiatry.

2014;48(10):917-931.

5. Montes-Mico R, Caliz A, Alio JL. Wavefront analysis of higher-order aberrations in dry eye patients. J Refract

Surg 2004;20:243-7

6. Uchino M, Schaumberg DA. “Dry Eye Disease: impact on quality of life and vision.” Curr Ophthalmol Rep.

2013; 1(2): 51-57.

7. Karakus S, Mathews PM, Agrawal D, et al. Impact of dry eye on prolonged reading. Optom Vis Sci. 2018

Dec;95(12):1105-1113.

Dr Scott Schachter founded Advanced Eyecare and Eyewear Gallery Optometry in

1994 in Pismo Beach, California. He has published and presented many papers on

the ocular surface, is a regular columnist for Optometry Times and Ocular Surface

News and is one of eight US global ambassadors for the Tear Film and Ocular Surface

Society (TFOS).

Hyaluronic acid for DED?

RESEARCHERS AT THE Brno

University of Technology in the

Czech Republic have embarked

on a study to investigate a new

raw material to make “better”

artificial tears.

Hyaluronic acid, produced by

the body and found mainly in skin,

the vitreous and the joints, already

contributes to the hydration and

lubrication of the tear film and

is known to reduce friction, said

study lead, Associate Professor A/Prof Martin Vrbka. Credit: Iveta Zieglová

Martin Vrbka from Brno’s Faculty of

Mechanical Engineering. “Unlike current preparations, which combine

various polymers to replace the individual properties of the tear film, we

are developing one polymer, based on a hyaluronic acid derivative.”

Initial work has been carried out into joint replacement therapies,

but now the team are developing an experimental eye model to

analyse the effect of their derivative on friction between the ocular

surface and the eyelid. The hyaluronic acid derivative also binds mucin

better to prolong any solution’s effectiveness, said Gloria Huerta-

Angeles from Czech biotech firm Contiro, which supplies a synthetic

form of hyaluronic acid.

Researchers hope to commercialise a better raw material for

artificial tears manufacturers within four years.

Tune in

and drop out…

Optima IPL technology provides a drug-free, drop-free

light-based treatment that reduces chronic inflammation

from debilitating conditions.

Patients with dry eye conditions can quickly and

comfortably be treated, markedly reducing their

reliance on ongoing eye drops.

If your patient suffers from dry eye

now’s the time to drop us a line…

For more info email info@southerneye.co.nz

or find the intro video on our LinkedIn page.

128 Kilmore Street, Christchurch

P: 03 355 6397

W: www.southerneye.co.nz

WWW.EYEONOPTICS.CO.NZ | 41


FOCUS ON EYE RESEARCH

Dr Mo Ziaei,

series editor

Amniotic membrane for DED

By Dr Rasha Altaie

DRY EYE DISEASE (DED) is a common ocular

surface disorder, resulting in one of the

most frequently encountered complaints

in ophthalmic practice. Whilst the disease is

complex and multifactorial, inflammation

is a common denominator in DED, which in

turn causes further damage to the corneal

epithelium and its underlying structures.

Several treatment modalities have been used

to suppress inflammation, however, results are

variable and the condition can be refractory

in some cases. The use of amniotic membrane

(AM) as another treatment modality in DED is

an exciting clinical development and novel area

of research.

AM is part of the amnion and consists of

a single layer of epithelial cells, a basement

membrane. Its utility in DED treatment

is attributed to its known potent antiinflammatory

properties. AM can either be

grafted in theatre with sutures or glue or can

be applied in an office setting. There are two

types of AM that can be used: cryopreserved

or dehydrated. They are proposed for use

with specific, typically severe or refractory

corneal and conjunctival disorders, including

persistent epithelial defect, prevention of

ocular complications associated with Stevens-

Johnson syndrome and primary or recurrent

pterygia. AM can also assist in wound healing

and in preventing scar tissue formation as it

has powerful antifibrotic and anti-scarring

properties but is not typically used as a

replacement for bandage contact lens use.

Treatment outcomes in the dry eye amniotic

membrane (DREAM) study

McDonald MB, Sheha H, Tighe S et al.

Clin Ophthalmol 2018:12 677–681.

Design: This published study highlights

the use of cryopreserved AM in DED. It is a

retrospective multicentre study completed

in the USA and has the largest number of

recruited cases to date. Patients with refractory

DED who received AM and completed at least

three months of follow-up were included. Data

collected were demographics; medical history,

including previous and current ocular treatment;

diagnosis; clinical presentations; comorbidity;

duration; and frequency of treatment with

cryopreserved amniotic membrane and

concomitant medications. The primary outcome

was the change in the 2007 TFOS Dry Eye

Workshop (DEWS) score after treatment.

Outcome: A total of 97 eyes of 84 patients

[12 (14%) male, 69 (82%) female, and 3 (4%)

unknown] were included in the study. Patients

exhibited severe dry eye (DEWS 3.25±0.5)

despite maximal medical treatments. AM was

applied at the office. The average duration of

AM placement was 5.4±2.8 days, with a range

of 2–11 days. AM was removed in 4% after two

days due to AM intolerance and one AM fell

out of the eye after two days. The overall DEWS

score was significantly reduced from 3.25±0.5

at the baseline to 1.44±0.6 at one week

(p


DRY EYE 2020

New MGD treatment holds promise

By Lesley Springall

A novel therapy for meibomian gland

dysfunction (MGD), developed from a

treatment for a chronic form of dermatitis and

dandruff, holds promise for a better solution

option for dry eye disease (DED).

AZR-MD-001, the lead product of

young, Israeli-Australian biotech company

Azura Ophthalmics, is the first ophthalmic

keratolytic for the treatment of lid margin

diseases such as MGD, blepharitis and contact

lens discomfort.

Research over the past decade has pointed

to hyperkeratinization, or the build-up and

shedding of the protein keratin into the

meibomian gland ducts, as a root cause of

obstructive MGD, the main cause of DED.

Currently, the only treatments for

MGD are considered both invasive and

cumbersome for patients, said Marc Gleeson,

Azura Ophthalmics CEO. “Technologies

designed to melt the meibum to help restore

the tear film lipid layer do not address

Marc Gleeson, CEO of Azura

the underlying causes of MGD, including

hyperkeratinisation, while mechanical

approaches targeted directly at hyperkeratinisation can be invasive and

unpleasant for patients. For this reason, they are unlikely to have broad

efficacy or acceptance across the general population, or prevent disease

progression in patients who are identified to be suffering from MGD

and/or altered lipid production.”

AZR-MD-001 is a novel ophthalmic formulation of the keratolytic

agent, selenium disulfide, which has been used successfully to treat

Continued from p42

Comment: The author concluded that self-retained cryopreserved-

AM implantation has a place in managing SS patients with severe

ocular surface disease, refractory to standard treatment. However,

the effects were found to be transient. Further, larger studies are

needed to confirm these benefits and a cost effectiveness study

would provide clinicians with a better understanding of where AM

transplantation fits in the already complex treatment paradigm

protocol for DED.

pityriasis versicolor, seborrhoeic dermatitis

and dandruff. “Selenium disulphide has a

triple mechanism of action, it slows down

keratin production, breaks down keratin and

increases the quantity of lipid produced by

the meibomian glands, a unique property of

selenium disulphide,” said Gleeson.

A non-ophthalmic formulation of the

active ingredient in AZR-MD-001 was

evaluated in a non-randomised, contralateral

eye controlled, phase I pilot study of 18

patients with MGD and evaporative DED.

The treatment was applied over the eyelid

margin for five minutes, twice weekly for 34

days followed by a single treatment on day

44. According to the company, significant

improvements in tear stability (tear breakup

time) and lipid layer quality for the drugtreated

eye versus the untreated contralateral

eye were observed by day 22 of treatment.

AZR-MD-001 was also considered safe and

well tolerated with controlled dosing, it said.

“These data suggest that a dermatological

approach can have a significant effect on

MGD and associated conditions by opening the glands, increasing lipid

production and restoring tear-layer health,” said Gleeson.

In a recent article in the journal Cataract and Refractive Surgery

Today (CRST), US-based cornea and refractive surgeon Dr Laura

Periman said, “The clinical science behind combined dermatologicophthalmologic

approaches to treatment of MGD is in its infancy, but a

treatment such as AZR-MD-001 represents an exciting new therapeutic

category in the development of strategies to address the obstruction

and hyposecretion problems of MGD.”

Following on from Azura’s placebo-controlled trial, which is

currently ongoing at the Sydney Eye Hospital, the School of Optometry

and Vision Science at the University of New South Wales and the

Department of Optometry and Vision Sciences at the University of

Melbourne, the company is enrolling patients in Australia and New

Zealand in a new prospective, multicentre, randomised, doublemasked,

vehicle-controlled, parallel group phase II study of AZR-

MD-001. Sites in Auckland include the Ocular Surface Laboratory

at the University of Auckland, Mortimer Hirst Optometrists and

Auckland Eye, and Rose Optometrists in Hamilton.

Azura expects to publish outcomes from its first trial in early 2021.

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WWW.EYEONOPTICS.CO.NZ | 43

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