Dry Eye 2016

SPECIAL FEATURE: DRY EYE
Characterisation of the ocular surface microbiome
BY GRANT WATTERS*
Understanding and managing ocular surface
disorders such as anterior blepharitis,
meibomian gland dysfunction and
dry eye disease remains challenging. Many of
these conditions, being chronic, recurrent and
debilitating, frustrate patients and clinicians alike
with a plethora of treatments that are, at best,
usually only partially effective¹.
As in the intestine, there is a growing belief that
dysregulation of the normal ocular commensal
microbiota population may contribute to many of
these conditions, so understanding the resident
ocular surface microbiome in normal and diseased
states may give us some clues as to whether we
could more accurately regulate these microbe
populations as a therapeutic strategy².
Extensive research into the role that bacteria
have in eyelid disease began with Thygeson’s work
in the early half of the 20th century. He identified
gram-positive (gm+) Staphylococcus aureus (S.
aureus) as the organism most frequently isolated
from the lid margins of blepharitis sufferers.
Author(s);
(year published)
Albietz & Lenton
(2006)
Graham et al
(2007)
Bowman et al
(1987)
Dougherty &
McCulley (1984)
Groden et al
(1991)
Watters et al
(2016)
Country N C-N S
(%)
S.Aureus
(%)
P.acnes
(%)
Corynebact.
sp.(%)
Subsequent studies showed that while S. aureus
was more common in blepharitis, coagulasenegative
Staphylococcus (C-NS) was the most
prevalent organism. Anaerobic gram-positive
Proprionibacterium acnes (P. acnes) was also found
to be more prevalent in eyes with lid disease 3,4 .
We* have recently completed a study across
three departments here at Auckland University
to characterise the ocular surface microbiome
present in New Zealanders with and without
eyelid disease. Inferior lid margin swabs were
collected from 157 randomly selected subjects
subdivided into three categories: no lid disease
(normal: n= 66); mild-to moderate lid disease (n=
41), and moderate-to severe lid disese (n= 50).
We also compared contact lens (CL) wearers and
non-CL wearers. All subjects were analysed for
aerobic isolates and 87 subjects were additionally
investigated for anaerobic bacteria (P. acnes) 5 .
Table 1. summarises our results in New Zealand
normal eyes compared to relevant overseas
studies. Of note is our sample exhibited a relatively
higher percentage of individuals with S. aureus, a
slightly lower incidence of C-NS, and an absence
of Corynebacterium
Streptococcus
sp.(%)
Australia* 18 84.0 6.0 22.0 6.0 0 6.0
Ireland* 12 81.0 0 19.0 19.0 6.0 6.0
Texas USA* 21 100.0 13.0 31.0 69.0 6.0 9.0
Texas USA* 47 95.7 8.5 87.2 63.8 - -
Florida USA* 160 87.5 15.6 73.7 45.0 - 4.3
New
Zealand*
39 64.1 48.7 25.6 0 0 5.1
Rubio (2004) Spain # 4366 56.8 6.4 - 30.2 7.5 6.2
Hsu et al (2013)
de Kaspar et al
(2005)
Capriotti et al
(2009)
Karthika et al
(2014)
Missouri
USA #
California
USA #
Sierra Leone
(Rural) #
India
(Rural) #
183 74.8 4.9 - 7.6 0.9 9.4
162 76.0 11.7 - - 4.9 6.8
276 28.6 19.9 - - - 16.0
100 32.0 10.0 - 11.0 2.0 -
Gm neg. rods inc.
Pseudomonas (%)
Table 1. Comparison of the ocular microbiome in different countries.
(-) denotes not measured; (*) denotes normal subjects in studies comparing normal and dry eye subjects;
(#) denotes consecutive and randomised “healthy” subject selection from the general population
spp. This could be due
to unique climatic
and environmental
conditions in New
Zealand affecting the
relationships between
these different
species. For example, a
Queensland, Australia
study showed higher
C-NS and lower
S. aureus counts
than New Zealand,
presumably due to
the warmer and more
humid climate 6 .
Anaerobic P. acnes has
previously been linked
with blepharitis and,
in our study, was the
second most prevalent
microorganism
isolated in subjects
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Staphylococcus aureus is the most frequently isolated bacteria from the
lid margins of blepharitis sufferers
with blepharitis after C-NS. This suggests that the
synergistic relationship between S. aureus, C-NS
and P. acnes changes between normal and diseased
states. We also found this was the case with CL
wearers, and other studies have found similar results
(7,8)
. Again our New Zealand cohort exhibited a
notable absence of Corynebacterium spp.
Further work is now being undertaken by
our group to target therapeutic treatments to
re-regulate the ocular surface microbiome for
the management of blepharitis, including the
development of a novel medical Manuka honeybased
extract acting as an antimicrobial and a mild
anti-inflammatory agent, (see P10).
BY GREG NEL*
Dysfunctional tear films have always
tormented me. The clinical signs of dry eye
disease (DED) and patient symptoms don’t
always seem to fit very well in my chair. Patients
who stain with lissamine and fluorescein aren’t
always the unhappy ones and vice versa. Even
more curious, contact lenses-associated dry eye
symptoms have some patients preferring to wear
the most illogical choices of lenses on occasion.
The worst part of everything is that, as
optometrists, we are supposed to be the ones
that know what is going on. I didn’t feel up to the
job and in the mid-noughties I declared war on
dry eye and made it a pet project.
The 2007 DEWS report (www.tearfilm.org/
dewsreport/pdfs/TOS-0502-DEWS-noAds.
pdf) helped identify a couple of key factors,
evaporation and osmotic change in particular,
but I needed to look at more than staining to
evaluate what was happening on the eye.
Critical signs included tear film meniscus
height, meibomian function and the meibomian
glands themselves. The lipid film thickness and
properties are also excellent predictors and
generally agree with the tear film surface quality
assessment (TFSQ) module on the Medmont
topographer. I had read papers on evaluating
the lipid film and that interference fringes could
be used to evaluate its thickness and character,
but hadn’t thought of this as clinically useful
To create your ping pong ball tearscope, cut the ball so that one
slit allows it to sit over the diffuser lens in front of the mirror
and another slit so that the widest beam illuminates the mirror
(brightest light)
References
1. Nelson JD, Shimazaki JM, Benetez-del-Castillo JM, Craig JP,
McCulley JP, Den S, Foulks GN. The International Workshop
on Meibomian Gland Dysfunction: Report of the Definition
and Classification Subcommittee. IOVS 2011; 52: 1930-37
2. Zegans ME, Van Gelder RN. Consideratons in
understanding the ocular surface microbiome. Am J
Ophthalmol 2014; 158: 420-422
3. Lee SH, Oh DH, Jung JY, Kim JC, Jeon CO. Comparative
ocular microbial communities in humans with and
without blepharitis. IOVS 2012; 53: 5585-93
4. Miller D, Iovieno A. The role of microbial flora on the
ocular surface. Curr Opin Allergy Clin Immunol 2009; 9:
466-70
5. Watters G, Craig JP, Swift S, Petty A, Turnbull P.
Characterisation of the ocular surface microbiome present
in New Zealanders with and without eyelid disease. Brit. J
Ophthalmol (in press)
6. Albietz JM, Lenton LM. Effect of antibacterial honey on
the ocular flora in tear deficiency and meibomian gland
disease. Cornea 2006; 25: 1012-19
7. Dougherty JM, McCulley JP. Comparitive bacteriology of
chronic blepharitis. Brit. J Ophthalmol 1984; 68: 524-28
8. Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley
JSG, Hayes VEA, Dartt DA, Downes CS, Moore TCB. Ocular
pathogen or commensal: a PCR-based study of surface
bacterial flora in normal and dry eyes. Invest.Ophthalmol.
Vis.Sci 2007; 48: 5616-23
* Grant Watters, MScOptom, a practicing Auckland optometrist
and a lecturer and researcher with the University of Auckland,
worked with Simon Swift PhD, Alex Petty BOptom, Philip
Turnbull PhD, BOptom and Associate Professor Jennifer
Craig PhD, MCOptom on the study. The researchers spanned
three departments: the Department of Ophthalmology, the
Department of Molecular Medicine and Pathology and the
Department of Optometry and Vision Science at the University
of Auckland, New Zealand.
Evaluating, treating DED and ping pong balls!
because tearscopes weren’t common outside the
research arena until a mis-focussed image of the
corneal endothelium yielded a spectacular image
of the tear film lipid layer. Experimentation and
improved cellphone cameras make this simple
to record on a regular basis. You get a great view
of the tear lipids by also using a ping-pong ball!
Incidentally, the modern ping pong ball is larger
than it used to be in an attempt to slow the game
down – even better for us! So, for just 75 cents at
your local sports shop (or mine anyway), you can
make your own tearscope. Just mount your ping
pong ball on your slit lamp’s diffuser after cutting
a couple of perpendicular slots in it with a Dremel
Tool or hacksaw blade – one to fit the diffuser and
one to get the slit beam to the diffuser.
Retroilluminating the lid with a transilluminator
and playing with the colour sliders in the slit lamp
camera software also gives great views of the
meibomian glands, superior to some of the infrared
systems I’ve tried. Encysted glands and gland
dropout and atrophy are far more common than I
had presumed. Imaging this is an excellent way of
convincing people of the need to actively manage
their lids on a day-to-day basis!
Another useful assessment is the use of
questionnaires; they are more sensitive as regards
symptoms in my opinion – we use the SPEED
(Standardised Patient Evaluation of Eye Dryness)
questionnaire, especially as your slit lamp diagnosis
is very situational, an “at-the-moment” snapshot.
IPL treatment has been a game changer for
many patients, both for dry eye symptoms and
contact lens intolerance. My criticism of this
quite futuristic intervention, however, is twofold.
Firstly, we still have to try it and see. As a
single intervention its success rate is impressive
and doesn’t hinge on patient diligence, but
exactly who benefits most remains as fractal as
dry eye disease itself. Patients with neuropathic
dry eye (mostly post-LASIK) and significant
meibomian gland dropout seem to have the
CONTINUED ON P5
a
b
Transilluminator meiboscopy
For further information call 0800 954 536 or email whitney@corneal-lens.co.nz
c
Examples of interference fringes: (a) thick, (b) disorganised and
unstable, (c) not too bad – some debris, (d) thin – notice vertical bands
d
Pre and post-IPL TFSQ over a MyDay contact lens in a symptomatic
patient, with improvement shown by the shallower gradient
indicating less rapid destabilisation
4 NEW ZEALAND OPTICS October 2016