Vol.14
No. 1, Januray, 2004
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.
