IT was the end of a great meeting
in Denmark. I had been lecturing
to Danish veterinary
ophthalmologists and enjoying
their great hospitality too. But the
best thing about such visits is the
contacts made and the new ideas
which make their mark.
A man I’d never come across
before made his way to the front of
the lecture
theatre and
produced
from his
pocket a tiny
tube of clear
gel (Figure
1). This, he
told us, had
been shown to speed the healing of
corneal ulcers in a recent scientific
study in rabbits, a copy of which he
held in his other hand.1
It was a polymerised hyaluronic acid gel which formed a scaffold
across the ocular surface, speeding the
healing of epithelial and stromal
ulcers. Had this been tried in a clinical
setting I asked – and did he have any I
could take and try? Only this one tube
he said apologetically. Never mind –
one was better than none, so I
whipped it out of his hand and asked
who had come up with the idea in the first place. A good end to an excellent
weekend conference!
How ironic then that Monday
morning brought a referral of a dog
with a long-standing stromal ulcer
which showed no signs of healing
(Figure 2). My normal treatment
would have been a surgical manoeuvre
– a pedicle graft or a hood flap. But
this elderly dog was not a good
anaesthetic risk and hey – I had the
answer in my pocket – or did I?
A drop of this gel twice daily
should have a beneficial effect, I told
the owner, but in these days of
evidence-based medicine here was a
treatment for which I really had no
evidence at all, but for the rabbit paper
I had printed out for myself by now. I
kept in touch with the dog’s owner
who said that the animal seemed more
than happy to have the drop of
soothing gel in his eye, and 10 days
later I was delighted to see a healed
cornea.
Granted, there was some corneal
oedema and migrated pigment onto
the surface but the dog had some
vision in the eye and the owner was
over the moon. In fact, he had only
used half of the tiny tube and brought
the rest back for my next case.
Having had
such success
with his dog, he
wanted to share
the gel with
another,
knowing that it
was the only
tube I had!
And sure
enough, the next week along
came a cat with
a similar non-
healing stromal
ulcer (Figure 3).
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
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.
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
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 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 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 re-
epithelialisation 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 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 long-
lasting scaffold across the ocular
surface is an ideal option for animals 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 cross-
linked 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.
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!
References
- Yang, G., Espandar, L., Mamalis, N.
and Prestwich, G. D. (2010) A cross-
linked hyaluronan gel accelerates
healing of corneal epithelial abrasion
and alkali burn injuries in rabbits.
Veterinary Ophthalmology 13: 144-150. - Williams, D. L. (2013) Topic-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. - 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
