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OPHTHALMOLOGY
VETERINARY PRACTICE FEBRUARY 2014
Speeding the healing of corneal ulcers
IT was the end of a great meeting
acid gel which formed a scaffold
in Denmark. I had been lecturing
across the ocular surface, speeding the
to Danish veterinary
healing of epithelial and stromal
ophthalmologists and enjoying
ulcers. Had this been tried in a clinical
setting I asked – and did he have any I
their great hospitality too. But the
could take and try? Only this one tube
best thing about such visits is the
he said apologetically. Never mind –
contacts made and the new ideas
one was better than none, so I
which make their mark.
whipped it out of his hand and asked
A man I’d never come across
who had come up with the idea in the
before made his way to the front of
the lecture
theatre and
Dr DAVID WILLIAMS
produced
discusses corneal ulcers and
reports on a new treatment for
from his
an ulcer extending into the
pocket a tiny
stroma and without a
tube of clear
predisposing cause in dogs which
gel (Figure
are not candidates for surgery
1). This, he
told us, had
been shown to speed the healing of
first place. A good end to an excellent
corneal ulcers in a recent scientific
weekend conference!
study in rabbits, a copy of which he
How ironic then that Monday
held in his other hand.1
morning brought a referral of a dog
with a long-standing stromal ulcer
It was a polymerised hyaluronic
which showed no signs of healing
continued from page 27
(Figure 2). My normal treatment
would have been a surgical manoeuvre
and quality of anaesthesia achieved
– a pedicle graft or a hood flap. But
with a 0.4% solution of this
this elderly dog was not a good
compound in healthy dogs, when
anaesthetic risk and hey – I had the
compared with the established topical
answer in my pocket – or did I?
anaesthetic tetracaine. Measurements
A drop of this gel twice daily
of the corneal touch threshold showed
should have a beneficial effect, I told
that the two topical anaesthetics were
the owner, but in these days of
similarly effective in reducing corneal
evidence-based medicine here was a
sensitivity but the oxybuprocaine
treatment for which I really had no
solution was less irritating to the
evidence at all, but for the rabbit paper
conjunctivae than tetracaine.
I had printed out for myself by now. I
American Journal of Veterinary Research
kept in touch with the dog’s owner
74 (10): 1,321-1,326.
who said that the animal seemed more
Systemic hypertension and
than happy to have the drop of
hypertensive retinopathy
soothing gel in his eye, and 10 days
following PPA overdose
later I was delighted to see a healed
cornea.
Jennifer Ginn and others,
Granted, there was some corneal
University of Wisconsin
oedema and migrated pigment onto
Phenylpropanolamine (PPA) was the
the surface but the dog had some
principal ingredient in some over-thevision in the eye and the owner was
counter decongestant and appetite
over the moon. In fact, he had only
suppressant products that were
used half of the tiny tube and brought
withdrawn from the US market in
2000. The authors describe the clinical the rest back for
my next case.
findings in an incident involving a
Having had
four-year-old spayed female Labrador
which ate 40 to 50 tablets containing
such success
the drug. On presentation within four
with his dog, he
hours of eating the tablets, it had
wanted to share
clinical signs of anxiety, piloerection,
the gel with
mucosal ulceration, cardiac arrhythmia another,
and mydriasis. It was also found to
knowing that it
have ventricular tachycardia and severe was the only
systemic hypertension and there was
tube I had!
hyphaemia and retinal detachment in
And sure
both eyes. Treatment with
enough, the
phenoxybenzamine, sotalol and
next week along
esmolol resolved the cardiac
came a cat with
abnormalities and the hypertension
a similar nonwas controlled with nitroprusside.
healing stromal
Journal of the American Animal Hospital
ulcer (Figure 3).
Figure 1.
Association 49 (1): 46-53.
Here the
problem preventing us from going to
surgery was a financial one: the owner
had come to us through our RSPCA
clinic run by the vet school to provide
help for owners with insufficient funds
for normal veterinary care and a
wonderful supply of first opinion
cases for the students.
In this little cat it was only seven
days before the owner triumphantly
brought the patient back just delighted
with the result. A completely healed
cornea with a tiny circle of opacity in
place of what a week before had been
one heck of a mess!
By now I had tracked down
Richard Koehn of Sentrx Animal
Health in Salt Lake City, Utah. I think
he was somewhat surprised to hear me
bouncing with excitement and
enthusiasm about his new product,
and asking for more so that we could
perform a proper clinical study.
These two cases, with ulcers which
hadn’t healed for 35 and 28 days but
then resolved in 10 and seven days
respectively, were almost statistically
significantly different in healing time
on their own at p=0.055 in a paired T
test, but we clearly needed more cases
to evaluate.
Remarkable results
Figure 2. Before and after treatment
of stromal ulcer.
someone with experience to evaluate
an ulcer, especially a deep one, to
determine what is best to be done?
You are risking a number of eyes
perforating if they aren’t treated
optimally.
And that certainly may be the case
in many ulcers. Every ulcer needs a
really careful assessment before
treatment can be decided upon. First,
what is the cause – is there an
underlying infection or a dry eye which
will need correcting before the ulcer
will heal, however good the magic
drops are? Secondly, is the ulcer
healing?
A superficial ulcer with a
devitalised epithelial edge where the
basal cells are not adhering to the
Soon more tubes of gel were winging
their way over the pond to me and our
study could begin in earnest. The
results were remarkable. In the first 15
cases, ulcers which had been referred
after failing to heal for an average of
25 days only took 13 days, again on
average, to heal. The statistical
significance of this was really
substantial.2
We had started to
call this gel DMD –
David’s Magic Drops
– as they seemed to
have a completely
novel effect on these
ulcers, many of which
would have gone to
surgery for a
conjunctival pedicle
graft or similar in the
past but now could
just be treated with
Figure 3. Before and after treatment.
this gel. It is soon to
be marketed by Bayer
– not, sadly, as DMD
but as Sentrx Remend,
the name it comes
with from its Salt Lake
City originators.
“Wait a moment,”
I hear other
ophthalmologists
saying. This sounds a
bit dangerous. Isn’t it
important for
VETERINARY PRACTICE FEBRUARY 2014
underlying basement membrane will
not heal unless the dead tissue is
removed, the remaining live tissue
encouraged to heal and the area
protected. In our study, these ulcers,
not surprisingly, did not heal with
Sentrx but only resolved after removal
of the devitalised non-adherent
epithelium and a stimulation of reepithelialisation using a grid
keratotomy or the newer diamond burr
debridement. More of that in a
subsequent article, I think!
Back to the assessment of an ulcer.
The other key feature of such a lesion
is its depth. If Sentrx Remend fails to
heal superficial non-adherent epithelial
erosions, the ulcers it excels in are
mid-stromal defects. It seems to be
creating a matrix, a scaffold, into
which the keratocytes can migrate and
produce new collagen to repair the
stromal defect.
The other ulcers where surgery is
still required are those where the
defect has progressed through almost
every layer of the cornea, just leaving
Descemet’s membrane intact. This is
the basement membrane of the
corneal endothelium and as such is
comprised of collagen type 4 and
laminin.
“Does that really matter?” you may
ask. Collagens normally have a glycine
Figure 4.
at every third amino acid, this allowing
the tight alpha helical structure.
Collagen type 4 lacks this regular
glycine and so forms sheets which can
expand since they are not regularly
covalently linked together.
It is this chemistry which allows
Descemet’s membrane to expand,
giving the classic descemeocoele
(Figure 4) which signals a cornea
ready to burst! Such a case calls for
reconstructive surgery and not merely
an eye drop. But for an ulcer
extending into the stroma and without
a predisposing cause such as dry eye,
Sentrx Remend may be just the
answer, especially in dogs which are
not candidates for surgery.
But it’s not only ulcers. A gel
formulation which produces a longlasting scaffold across the ocular
surface is an ideal option for animals
OPHTHALMOLOGY
with dry eye. Now again, the optimal
treatment for keratoconjunctivitis
sicca is topical cyclosporine in
Optimmune, with the aim of
increasing the eye’s production of its
own tears.
But not every eye with KCS
responds to the immunomodulatory
effect of cyclosporine. It is in these
cases where an effective tear
replacement drop is required and
Sentrx Remend fills this requirement
admirably. We compared the crosslinked hyaluronic acid of Remend
with a standard HA drop in 25 dogs
with cyclosporine-resistant dry eye.
Remend was significantly better than
the standard HA tear replacement
drop when we compared ocular
redness, irritation and discharge after
twice daily medication.3
So when Bayer market Sentrx
Remend in the UK, look out for
David’s Magic Drops for corneal
ulcers and dry eye in the canine eye
and try them out for yourself!
1. Yang, G., Espandar, L., Mamalis, N.
and Prestwich, G. D. (2010) A crosslinked hyaluronan gel accelerates
healing of corneal epithelial abrasion
and alkali burn injuries in rabbits.
Veterinary Ophthalmology 13: 144-150.
2. Williams, D. L. (2013) Topic-
29
ally applied cross-linked hyaluronic
acid polymer accelerates healing of
corneal stromal ulceration in the dog.
American College of Veterinary
Ophthalmologists conference
proceedings, Puerto Rico.
3. Williams, D. L. and Mann, B. K.
(2013) A Crosslinked HA-Based
Hydrogel Ameliorates Dry Eye
Symptoms in Dogs. International Journal
of Biomaterials 460437; doi:
10.1155/2013/460437
David L. Williams, MA, VetMB, PhD,
CertVOphthal, CertWEL, FHEA,
FRCVS, graduated from Cambridge in
1988. He then worked at the Animal
Health Trust before gaining his
certificate in veterinary
ophthalmology and moving to the
RVC to undertake a PhD. After this he
stayed at the RVC as resident in
clinical pharmacology with a particular
interest in ocular pharmacology. After
two years he moved back to the AHT
for a period as clinical investigative
ophthalmologist before returning to
Cambridge where he is now associate
lecturer in veterinary ophthalmology,
a position he combines with teaching
at St John’s College, where he is
director of studies in veterinary
medicine and college lecturer in
pathology.
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