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Basilio
Colligris,
Jesús
Pintor

(ClinicalTrials.gov
Identifier:
NCT01250171).
The
study
reports
suggest
that
both

substances
are
well
tolerated
in
most
patients,
and
no
serious
adverse
effects
have

been
reported.
The
drugs
provide
significant
advantages
over
existing
competitive

therapies,
including
bimonthly
administration
and
an
approved
use
in
children

(40-­-42).

MIM-­-D3

Mimetogen
Pharmaceuticals
Inc.
is
developing
MIM-­-D3,
a
small
molecule

mimicking
the
nerve
growth
factor
(NGF)
activity
(Figure
5).
NGF
stimulates
the

conjunctival
cell
glycoconjugate
secretion
and
during
in
vivo
trials
demonstrated

therapeutic
efficacy
on
dry
eye
disease
(43).
NGF
plays
an
important
role
in
ocular

surface
maintenance,
corneal
wound
healing,
displaying
a
mucin
secretagogue

activity
in
conjunctival
cells
(44).
Jain
and
colleagues
during
evaluation
studies

demonstrated
that
a
1%
MIM-­-D3
dose
increased
glycoconjugate
concentration,

improving
the
quality
and
stability
of
tear
film
and
the
healing
on
the
ocular

surface
in
dry
eye
(45).
Mimetogen
conducted
Phase
II
safety
and
efficacy
studies

(ClinicalTrials.gov
Identifier:
NCT01257607)
from
December
2010
to
October

2012,
on
150
patients
with
the
application
of
1%
MIM-­-D3
and
5%
MIM-­-D3
for
28

days.
Unfortunately
the
target
primary
endpoints
were
not
met
completely.

Despite
this
negative
development
the
company
continues
the
development

considering
MIM-­-D3
as
a
potent
compound
(46).

DIFLUPREDNATE

Alcon
is
evaluating
the
corticosteroid
Difluprednate-­-Durezol,
a
butyrate

ester
of
6(alpha),9(alpha)-­-difluoro
prednisolone
acetate
as
a
potential
treatment

for
dry
eye
disease
(Figure
6)
(47).
This
corticosteroid
is
preventing
the

phospholipid
release
and
decreases
the
eosinophil
action.
Durezol
received

approval
from
the
FDA
in
2008
as
the
first
ophthalmic
steroid
for
the

postoperative
inflammation
and
pain.
Alcon
started
clinical
trials
Phase
II

(ClinicalTrials.gov
Identifier:
NCT01276223)
in
January
2011
for
the
Difluprednate

ophthalmic
emulsion
0.05%,
one
drop
in
each
eye
twice
per
day,
on
726
patients,

as
an
anti-­-inflammatory
treatment
of
dry
eye
disease.
Mulki
and
colleagues
are

suggesting
that
difluprednate
0.05%
ophthalmic
emulsion
exhibits
enhanced

penetration,
decent
bioavailability,
rapid
local
metabolism
and
strong
efficacy,

with
a
low
incidence
of
adverse
effects
and
a
comparable
safety
profile
(48).

158