The
Role of Topical Amiloride and
Flurbiprofen in Healing and
Neovascularization of Corneal Ulcers
Rajender S Chauhan, RC Nagpal,
Mridul Choudhary
INTRODUCTION
Corneal ulcer is defined as
discontinuity in the normal
epithelial surface of the cornea
associated with necrosis of the
surrounding corneal tissue. Corneal
ulcer can be due to bacterial,
viral, or fungal infection,
concomitant with systemic,
dermatological, or connective tissue
disease, chemical or thermal injury,
and nutritional deficiency.
Neovascularization is a common
finding as a part of the healing
process in the body. The growth of
capillaries into the cornea from the
limbal vascular plexus is referred
to as corneal neovascularization.
The conditions which can produce
neovascularization are infections
which may be bacterial, viral, or
protozoal, and non infectious
disease processes like
Steven-Johnson syndrome, rheumatoid
arthritis, atopic
keratoconjunctivitis, graft
rejection, trauma, chemical burns,
contact lens wear etc.
Neovascularization is an active
process that is designed to heal the
once avascular cornea. It has
excellent healing effect. The
unfortunate aspect of this process
is that the vascularization of the
cornea is associated with decreased
visual acuity, increased risk of
graft rejection, and a greater risk
of opacification from deposition of
lipid.
An early
step in the angiogenesis is lysis of
extra cellular matrix at the edge of
new vessels. Plasminogen activators
are enzymes, which by converting
plasminogen to plasmin activate the
proteolytic cascade that digests the
extra cellular matrix. The diuretic
Amiloride is a competitive inhibitor
of plasminogen activator, and has
been shown to inhibit corneal
neovascularization and accelerate
ulcer healing when given topically.
This has encouraged us to see its
effect in human eyes with corneal
ulcer and neovascularization.
MATERIAL AND METHODS
A double blind clinical trial was
conducted in patients of bacterial
corneal ulcer with
neovascularization attending the OPD
of the upgraded Department of
Ophthalmology, Pt. B.D.Sharma PGIMS,
Rohtak and then admitted in the Eye
ward.
45
patients of bacterial corneal ulcer
with neovascularization were divided
into 3 groups by randomization, and
received one of three drugs labeled
A, B, or C.
Among
the three drugs were topical
Amiloride (1%), Flurbiprofen
(0.03%), and artificial tear drops
as control.
Area of
corneal ulcer and neovascularization
were measured on slit lamp on day 0,
7, 14, 21 and 30 days.
The size
of the ulcer was determined by slit
lamp biomicroscopy measurement of
largest diameter and the
perpendicular diameter. The area of
the ulcer was determined as: IIab/4
(Fig-1)
Area of
Corneal neovascularization was
measured in mm2. Maximum
extent to which neovascularization
reached in each pie shaped area = a
in mm.
Radius
of cornea = b in mm.
Radial
distance of area free from
neovascularization = b - a = c
Therefore area of neovascularization/6
(b2-c2) (Fig-2)
OBSERVATIONS
Table showing average rate of
corneal ulcer healing and rate of
regression of corneal
neovascularization in groups 1, 2,
and 3.
|
Group |
Avg. rate of corneal ulcer
healing (mm2/day) |
Avt. rate of regression of
corneal neovascularization
(mm2/day) |
|
Group 1 (drug A) |
0.514 |
0.54 |
|
Group 2 (drug B) |
1.71 |
4.9 |
|
Group 3 (drug C) |
0.92 |
1.99 |
The
results were anlysed by comparing
drug B with drug A and C, drug C was
also compared with drug A. Unpaired
't' test was used for statistical
analysis and p value was found to be
significant (<0.01).
Drug A
was artificial tear drops, drug B
was 1% amiloride, and drug C was
flurbiprofen (0.03%).
In one
patient of the amiloride group,
there was no regression of
neovascularization.
DISCUSSION
A key step in angiogenesis is
production by endothelial cells of
serine proteases like urokinase
plasminogen activator and matrix
metalloproteinases which degrade the
basement membrane and permit
endothelial invasion of
extracellular matrix. Since
amiloride inhibits urokinase
plasminogen activator and thus
inhibits conversion of plasminogen
to plasmin, it prevents degradation
of basement membrane and
extracellular matrix. Acceleration
of ulcer healing and
neovascularization is explained on
the basis.
Our
study shows that 1% amiloride
accelerates healing and regresses
neovascularization in corneal ulcer
patients as compared to topical
0.03% flurbiprofen and artificial
tear drops. The difference was
statistically significant in both
the groups. The one patient who did
not respond to amiloride therapy was
one in whom the ulcer progressed
very fast, leading to descemetocele
formation and perforation.
CONCLUSION
1% topical amiloride accelerates
healing of corneal ulcer and causes
regression of neovascularization in
patients of corneal ulcer. But
further studies are needed to
evaluate and compare effects of
various concentrations of amiloride
to find out the minimum effective
therapeutic concentration. In
future it may prove to be a good
ulcer healing and
anti-neovascularization agent.
Address
for Correspondence
Dr. R.S.
Chauhan, Deptt. of Ophthalmology,
Pt. BD Sharma PGIMS, Rohtak.
