ABSTRACT

Purpose : this study aims to compare the effectiveness of latanoprost and dorzolamide to the
progressivity of the thinness of Retinal Nerve Fiber Layer (RNFL) on patient with Normotensive
Glaucoma
Method : A comparative experimental study was conducted on two group of Glaucoma
Normotensive patient, the group was given latanoprost and dorzolamide which meets the
inclusion criteria, the evaluation of RNFL thickness was conducted using Stratus OCT after 3
month of therapy. The result then statistically analyzed.
Result : 16 samples of eye with normotensive glaucoma were obtained, 8 of them were given
latanoprost therapy and the other 8 were given dorzolamide. The latanoprost group consisted
with average age of 54.75 years, IOP 10.50 mmHg and CCT 547.12 µm. The dorzolamide group
consisted with average age of 56 years, IOP 11 mmHg and CCT 547 µm. The statistically
analysis for the comparison of latanoprost and dorzolamide tested with t-test to the thinness of
RNFL for inferior quadrantt (p=0.237), nasal quadrantt (p=0.253), and Man-Whitney RNFL test
to the superior quadrantt (p=0.713) were not statistically significant. The t-test result for the
comparison of latanoprost and dorzolamide to RNFL temporal quadrantt (p=0.024) was
statistically significant.
Conclusion : both Latanoprost and dorzolamide were effective to prevent the thinness
progressivity of RNFL especially the inferior, superior and nasal quadrantts.
Keyword : Latanoprost, Dorzolamide, RNFL, OCT

Chapter I progressive optic neuropathy. Normal

PREFACE
Background
Glaucoma is consider to affected
more than 67 million people around the
world, where around 10% or 6.6 million of
them estimated to have blindness. Glaucoma
is the most common cause for the world
irreversible blindness and second to cause
blindness after cataract. Glaucoma is
responsible to 14% of the world blindness.
In United States, chronic open angle
glaucoma (COAG) affected more than 2.2
million people and this number projected to
increase to 3.4 million in 2020.1,2
Glaucoma cases are estimated to
reach 80 million cases in 2020 where 74%
of those are Primary Open Angle Glaucoma
(POAG). POAG is a disease characterized
with optic disc cupping enlargement and
loss of vision, asymptomatic, and
Tension Glaucoma (NTG) is a variation of
POAG where clinically the IOP is less than
21 mmHg which related to Glaucomatous
optic neuropathy and also related to the
changes of visual field. The Japanesse
population has a high incidence of NTG.
The fact that in a study a 92% of NTG was
obtained. A study on February 2009 to the
Japanesse American in San Francisco found
that the proportion of NTG patient were 4
times higher than the High IOP glaucoma.3
The socioeconomic impact of
glaucoma is enormous but difficult to
quantify. The economic database of
glaucoma cost is limited. The total direct
cost for each COAG or ocular hypertension
patient for two years after diagnosis on
average are around 2.109 dollar in USA and
around 2.160 in Sweden. The costs are
seems higher for advance cases, the
uncontrolled disease and on cases with
trabeculectomy procedure.4
 The increase of IOP, visual field
defect and changes in optic disc are the
primary sign of POAG, but these three signs
are not always exist simultaneously. Some
researcher has investigated the early sign of
glaucoma. It was established that the
thinness of RNFL are precedes the
functional lost, especially the function of
visual field vision which detected by
perimeter examination. Glaucoma patients
have thinner RNFL compare to normal
people and the relationship between the
RNFL thinning with visual field defect has
been widely studied. The tool used to
measure the thickness of RNFL is optical
coherence tomography (OCT).
Latanaprost 0.005% as a single daily
dose has shown the benefits of decreasing
Intraocular pressure (IOP) on patient with
POAG or ocular hypertension and does not
adversely affect the heart and lung
associated with the used of beta blocker
agent. Therefore latanoprost has added
value as a first-line treatment option on
patient with open angle glaucoma or ocular
hypertension.5,6
Hydrochloride dorzolamide is the
first carbonic anhydrase topical which used
in clinic that work to lower IOP by
decreasing the production of Aqueous
humor. Dorzolamide does not exhibit an
acid-alkali or electrolyte disturbance as well
as severe systemic side effect compare to
oral or intravenous carbonic anhydrase
inhibitor, as well as beta adrenergic agonist
which are contraindicated for asthma or
heart disease.7
Formulation of the problem
Based on the background the author
can formulate the problem as follow
:whether latanoprost is more effective in
preventing the thinning of RNFL compared
with dorzolamide in Normal Tension
Glaucoma ?
Research Purposes
The aim of this study is to know the
effect of latanoprost and dorzolamide to the
thinning of RNFL in patient with Normal
Tension Glaucoma .
Research Benefit
To know which drug that is effective
in treating patient with nor agesmo tension
glaucoma.
Chapter II
THEORITICAL REVIEW
Prevalence
The prevalence of open-angle
glaucoma has considerable variation
between ethnicity and race. "Baltimore eye
survey prevelence COAG" research in
people over 40 years of age was
significantly higher in African (4.7%) than
Caucasian (1.3%). Hispanic prerequisite in
the United States of 2.0% for over 40 years,
as well as those found in other studies for
Caucasian patients of the same age range.
The prevalence of COAG among Asian
populations varies widely, which generally
has the same level of prevalence as
Caucasian (Chinese in Singapore, 2.4%,
Japanese 2.6%, Tamil nadu 1.7%) and other
populations (Mongolian, 0.5% alaska, 0.1%
) has a low rate. Age invoices have a strong
influence on the prevalence of COAG
compared to race and ethnicity.
Definition of open angle
It is still controversial whether
normotension glaucoma represents a
different disease from or equal to POAG
regarding the average intraocular pressure
(IOP). Because IOP is a continuous variable
without a normal dividing line between
normal and abnormal, many experts believe
that differences in terms of low-pressure
glaucoma and normal-pressure glaucoma
should be left out. But this debate tends to
be preserved.
The Possible Mechanism of Open Angle
Glaucoma
A. Intra ocular effect
Although NTG can be differentiate
from COAG by the IOP that does not exceed
21 mmHg, the pressure tend to slightly
higher than the normal population. There are
three studies showing the significant
influence of IOP to the progressivity of
neuroretinal rim damage in NTG. In 2
studies of NTG patient with asymmetry IOP,
the loss of visual field vision is the typical
bad sign on the eye if the pressure higher. A
random study that compare between NTG
patient treated with anti glaucoma agent and
which are not treated showing that in the
group that have been treated occurs
protection of the visual field and the neural
status around 30% compare to those who
don’t treated. Therefore, the IOP concept are
confirmed to be the cause of Optic
Neuropathy on NTG.9,10,11
B. Ocular Vascular Disorder
Drance et al. describing 2 form of NTG:
(a) the non-progressive, usually related to
transient vascular shock episode, and (b)
the progressive, consider to be resulted by
optic nerve head vascular insufficiency.
Hayreh support that NTG is different from
anterior optic neuropathy ischemia due to
more acute process. Several studies related
to the invention covers hemodynamic crisis,
total bilateral carotid internal artery
occlusion, the narrowing of focal arterioles
around optic nerve, and the increasing of
vascular resistance of ophthalmic artery.12,13
C. Systemic Vascular Disorder
Patient with NTG has a higher nocturnal
pressure than normal people.14 A more than
24 hours echocardiography examination
shows a significantly greater asymptomatic
myocard infarction in patient with NTG
(45%) compare to normal subject (5%),
accompanied with ischemic episode in the
night.15,16,17
NTG patients recorded to have an
increased headache frequency with or
without migraine. Several other studies
failed to confirmed this relation, which 1/3
of the study obtained that NTG patients with
significant headache have a lower IOP than
those without headache. The reducing of
blood flow in fingers, especially in response
to cold exposure had been reported although
one study failed to confirmed this finding.18
The hematology disorder was reported
related to NTG include blood pressure and
plasma viscosity and hypercoagubility (ex.
Increasing of platelets adhesion and the time
of euglobulin lysis). Hypercholesterolemia
was also been reported higher in NTG
patients. MRI result of NTG patients
revealed an increasing incidence of diffuse
cerebral ischemia which proved the vascular
caused.19
Systemic Pathogenesis and Evaluation
Clinical description that observed in NTG
patient are often hard to distinguished from
POAG. The pathofisiology and etiology of
NTG as the same as POAG are still hard to
understood. The lowering of IOP by surgery
or medication reduce the risk for progressive
glaucoma damages on NTG patient which
proved that IOP has a significant role in the
pathogenesis of the disease. NTG and
POAG have a multifactorial disease process,
but the dependent and nondependent IOP are
also the key factors. It is obvious that most
NTG eyes have greater independent IOP
role. On NTG, another unique relation have
been investigated and contributing as a
pathogen risk factor.19
A. Sleep apnea syndrome
The repeated obstruction of
respiratory airway during sleep can
caused hypoxia. It has been a decision
that the disruption of autoregulation of
blood flow to optic nerve can occur and
cause apoptosis of retinal ganglion cell
(RGC). The prevalence of NTG among
patient with sleep apnea obstruction
syndrome is increased significantly
compare to normal person.20
B. Blood pressure
Systemic blood pressure is also has a
relation to the event of NTG which
affected the ocular blood flow. In the
Baltimore survey, the low diastolic
perfusion pressure closely related to the
prevalence of glaucoma. The Low-
pressure Glaucoma Treatment Study
(LoGTS), related to systemic
hypertension, obtained that those who
got anti-hypertension drugs, the
incidence was 44.2% (n=190), as the
same as the other study. The NTG
subject was report to have lower
systemic blood pressure. The prevalence
episode of hypotension and functional
vasospasm accompanied with optic
nerve hypo-perfusion was also
21
reported.
C. Migraine and Vasospasm
Phelps and Corbett was conducted a
case-control study in 1985 to the events
of migraine on NTG. They obtained
result that the history of migraine on
NTG patient was 37% higher than those
obtained in normal group or POAG
patients (estimated 22%). Possible
linkage of migraine with NTG was an
indirect evidence that blood flow
disorders that may be caused by
vasospasm or autoregulation disorders
may play a role in NTG. Endothelin-1
(ET-1) is a vascular endothelium derived
vasocontricting peptide thought to be
involved in some vasospastic disorders
In the presence of cold exposure, plasma
ET-1 levels increased significantly in
glaucoma patients compared with
healthy controls associated with
decreased visual function and vasospasm
induced by ET-1.
D. Disk Bleeding
Optical disc bleeding occurs in
patients with all types of glaucoma, but
most bleeding is obtained in the eyes of
NTG. Furthermore, disk optical bleeding
is a risk factor for the deterioration of the
field of view. Disk bleeding is caused by
mechanical damage from optical disks,
especially in the lamina region of the
kribrosa causing mechanical trauma to
capillaries that resemble optical disks.
The blood vessel rupture of the eyes
marked by elevated IOP is tamponade,
leading to very small extravasations of
clinically detectable blood volume
different from NTG where the
tamponade mechanism does not occur.
E. Autoimmunity
There are several reports that
indicate that autoimmune may play a
role in glaucoma. Autoantibodies of
some antigens are found in patients with
glaucoma in higher concentrations of
healthy people. The phosphatidylserine
antibodies, α-fodrin, and some other
protein antigens, have been found in
NTG patients. The presence of these
antibodies is a sign of an optic nerve
injury on glaucoma.24
The General Principle of Treatment to
Lowering Intraocular Pressure
Because of the large proportion of
untreated patients with NTG eye over a 5-
year period of asymptomatic disease, this is
a reason to closely observe patients with a
mild loss of field of vision before initial
therapy. It is important to document intra-
ocular pressure without therapy to establish
pressure targets. Intraocular pressure should
be measured at least 3 separate times,
especially the diurnal curve. A 30% under
average drop of intra-ocular pressure that is
not treated is a reasonable initial target. In
patients without contra indications, usually
in the first use is prostaglandin analok,
accompanied by laser trabeculoplasty as an
alternative therapy. Topical carbonic
anhydrase, B-adrenergic agonist, and a2-
adrenergic agonist can be used as a primary
or additional agent.
Symptoms and Signs of NTG
Increasing of intraocular pressure is
an important risk factor in the development
of glaucoma, but this is not the only risk
factor. In Normal Tension Glaucoma , other
risk factors are generally not known with
certainty in playing an important role. Many
researchers propose a hypothesis that
vascular factors are a significant part of the
development of this disorder. Some studies
have shown that normal-pressure glaucoma
patients show a high prevalence due to
vasospastic disorders such as headache
migraine and raynaud phenomenon,
ischemic vascular disease, autoimmune
disease, and coagulopathy when compared
with high-pressure glaucoma. Vascular
autoregulation defects had been explained in
the study on NTG. This condition marked
with bilateral and progressive, although
sometimes the IOP was normal. Several
studies explained that although the pressure
was normal but the IOP weren’t the same
between the two eyes, and the worst damage
affect the eye with higher IOP. The
Collaborative Normal Tension Glaucoma
Study (CNTG) obtained that the lowering of
IOP at least 30% will reduce the
progressivity of visual field defect from 35%
to 12%, it is confirmed that IOP was
definitely have a role in this condition.25
The visual field defect of NTG is
tend to be more focal, deeper, and closer to
fixation, especially in the early stage of the
disease, compare to the usually seen in
POAG. Several other signs are like optic
disc hemorrhagic, the thinning of neuro
retinal rim especially in inferior quadrantt
and inferotemporal are also been found in
NTG compare to POAG.
Picture 1. Optic disc cupping, disc
hemorrhagic on patient with Open angle
Glaucoma
Anterior Chamber Evaluation
To assess the depth of anterior
chamber, we can use slit lamp with 600
angle to evaluate the distance between iris
and posterior cornea which is known as the
Van Herick method.26
Table 1. The comparison of Anterior
chamber depth to the thickness of cornea
and the estimates interpretation of Anteror
chamber.
Gradation The Interpretation
comparison of
Anterior
chamber depth
to the thickness
of cornea
4 1:1 ore more Anterior chamber
 estimated
between 35o-45o
3 1: ½ Anterior chamber
estimated
between 20o-35o
2 1: ¼ Anterior chamber
estimated 20o
1 1: < ¼ Anterior chamber
estimated 10o
0 Closed Anterior chamber
0o
Gonioscopy and Interpretation
On the use of indirect gonioscopy, a
clinician should have known the landmark
of the angle. It is important to do the
gonioscopy inside darker room. A small slit
to minimalized the amount of light to the
pupil that can cause pupillary constriction
and change the image of peripheral angle
and can show the false open angle and right
identification ode narrow angle or closed
angle. Scleral spurs and Schwable line are
the most consistent structure. The use of slit
and précises focus, the examiner can see the
mirroring of 2 line, 1 from the outer layer of
cornea and the relation to sclera and the
other form of is inner layer of cornea.
Scleral spurs is a thin, pale line between
ciliar surface and pigmented area of the
trabecular meshwork. The inferior angle
generally wider and an easy area to localized
the landmark. A closed angle, when
peripheral iris is clogging the trabecular
meshwork until there is no visualization on
gonioscope. The wide angle is determined
by the insertion of iris on the ciliary surface
and iris’s curvature.26 The structure which
can be evaluated in the angle determination
is ciliary body band, which is the most
posterior part that looks more light pink to
light brown. The width depends on the
position of insertion and tends to be narrow
in the hypermethropia and width of the
myopia. Scleral spurs are the most anterior
projection structures of the sclera and the
sides attached with the longitudinal muscles
of the ciliary body. On examination
gonioskopi this structure is at the back of the
trabecular meshwork and shiny white color.
This section is an important benchmark
because it is relatively constant in different
eyes. Trabecular meshwork, is a structure
between spurs and grayish-blue schwalbe
line. The front is bordered by schwalbe line
and glossy white. Schwalbe line, is the
structure of the front line that looks white.
The width of the angle can be determined
based on the gradient and angle according to
the Shaffer system are as follows: 27
1. Gradient 4 (35-45˚) is the widest
angle in which the cilliary body band
looks easily seen.
2. Gradation 3 (25-35˚) is an open
angle where the visible structures
start from the spurs sclera and other
anterior structures.
3. Gradation 2 (20˚) is a moderately
narrow angle, where the visible
structure is trabecular meshwork.
4. Gradient 1 (10˚) is a very narrow
angle in which only the visible
schwable line structure is visible.
5. Slit angle is a state where no visible
straps are visible.
6. Gradation 0 (0˚) is a closed angle
caused by the iridocorneal
attachment.27
The Role of Optical Coherence
Tomography (OCT) in Glaukoma
The Invention of OCT have been
opened our knowledge of diagnosing
glaucoma, especially in the analysis of retina
nerve fiber layer (RNFL) through OCT
assessment, with 10µm resolution allows
doctor to measure peripapillary RNFL
thickness, the investigation of the losing half
part or the width of RNFL which is the
clinical prove of biomicroscopy
examination.
 It has been decided that the sign of
RNFL losing often can be detected in
glaucoma before losing the visual field that
is measured by standard perimetry and
before the changing of optical nerve can be
seen. The ability of OCT stratus to provide
the measurement of RNFL structure is well
enough to assess early detection of
glaucoma. It is certainly needed to analyzed
the OCT result in the context of RNFL
analysis that is important to support
diagnosing glaucoma.
The OCT stratus analysis often used
in the analysis RNFL thickness in the
glaucoma, RNFL mapping and analyzing
optical nerve. Analyzing the thickness of
RNFL and mapping RNFL are the basic
thing in the optical disc imaging.
RNFL Interpretation
The assessment and interpretation of
the printed RNFL need systematical
approach, to be able to measure the average
of that in the table and graphic. This
measurement is important because of the
early detection of glaucoma and the degree
of the severity related to the RNFL thickness
measure.
Table.2 The standard measurement of
average RNFL thickness in the glaucoma
assessment
> 80 um Normal
70-79 Glaucoma suspect
60-69 Early Depletion, Early
Glaucoma
50-59 Moderate Depletion,
Moderate Glaucoma
40-49 Advance depletion,
Advanced Glaucoma
<30 Advance depletion,
Primary retina disease
The depletion until the losing of
RNFL in the inferior quadrant and superior
quadrant are the important indicator of the
etiology of the disease. The average normal
measure of RNFL superior is 142.7 which in
the early glaucoma become less than 104.8
µm. The average normal measurement in the
inferior is 148.6 µm and decrease till less
than 103.9 µm in the early glaucoma.
The assessment indicator that also
can assess RNFL is quadrant plot, which is
360o field and divided by 4 of 90o field for
each of inferior quadrant, superior, medial
and temporal. While sector plot of each field
of 30o to assess focal defect especially in the
inferior and superior region. In the printout
result will also be seen TSNIT plot in the
form of graphic which can provide
information by qualitative and quantitative
about peripapillary RNFL.
The disappearance of RNFL can be
detected before visual field defect exist in
perimeter assessment and also before the
occurrence of the classic signs of glaucoma
in the optical nerve. Glaucoma generally is a
“focal disease” with predilection in the
inferior disc and superior RNFL. This area is
an initial site that under goes changes and if
often difficult to see clinically.31
Retinal Nerve Fiber Layer (RNFL)
The axon passing through the retinal
nerve fibers from the ganglion cells to the
optic nerve head, the axon are distributed in
a distinctive pattern. Peripheral temporal
fiber originating from either the side of the
horizontal centerline, the median raphe and
the curve above or below the fovea as the
arcuate nerve fibers, while from the retinal
center of the papillomacular fibers, and the
nasal fibers though directly to the optic
nerve head.
The understanding of anatomy is
important because it relates to the type of
field defect in glaucoma. The arcuate nerve
fibers occupy the superior and inferior parts
of the optic nerve, with the axons of the
peripheral retinas occupying parts of the
optic nerve. Arcuate fibers are most
susceptible to early glaucomatous damage.
The dispersed papillomacular fibers are
estimated to exceed 1/3 of the distal optic
nerve, especially the inferotemporal in
which the density of axon is higher. The
Nerves looks like overlaping with
extramacular nerve which is can explain the
stand of central vision during early
glaucomatous optic atrophy in this area.
Picture.3 Arcuate Scotoma (Bijjerum) in 10-
20° from fixation area. The damage of
glaucomatous nerve which contains axon in
inferonasal and inferotemporal retinal area
cause arcuate defect. Scotoma often begin as
a missing single area and then become
wider, deeper and multifocal. (Visual field
courtesy of G.A Cioff; MD), courtesy from
glaucoma textbook, AAO 2011, page. 61.
Latanoprost
Prostaglandin analog was
hypotensive lipid agent and divided in two
categories its prostamide and decosanoid.
Now there are four prostaglandin analog that
been using in clinic: Latanaprost, travapost,
bimatoprost, dan isopropyl unoproston.
Latanaprost was F2 prostaglandin Alfa that
reducing intraocular pressure with
increasing the uveoscleral outflow.
The True Mecanism of this drug that
increased uveoscleral outflow is unknown.
The Uveoskleral outflow across extracelullar
cilliary body chamber and then through the
supracoroid chamber and reached the
posterior pole part of the eye. Prostaglandins
activated the prostanoid receptors of ciliary
muscle and trigger several local responses
like formation of cAMP. This signal will
excite biosynthesis of metalloproteinase
matrix that can breaks extracellular matrix
molecules. This enzyme initiate the
transformation of collagen on ciliary muscle
therefore increased the space of ciliary
muscle fibers and then reduced hydraulic
resistance of uveoscleral flow. Latanoprost
is able to penetrate cornea and becomes
active after hydrolization of corneal esterase,
and this medicine is able to lowering
intraocular pressure by 25-32%.
Administration of this drugs only once a day
and given at night and less effective if used
twice a day. The lowering of intraocular
pressure by latanoprost is 0.005% ended up
after 24 hours of single dose administration.
Patient with ocular hypertension or open
angle glaucoma, administered with one drop
of latanoprost solution 0.005% (~1.5
micrograms) given topically per day to
lowering diurnal TIC from 22% to 39% until
12 months of treatment with control
regularly.
Latanoprost 0.005% as single dose
given daily shown benefit of lowering
intraocular pressure on open angle glaucoma
patient or oculus hypertension and did not
give any bad influences on heart and lungs
in relation with the use of betablocker.
Therefore latanoprost has more value as the
choice of first-line therapy of open angle
glaucoma or oculus hypertension patient.
The ocular side effects are the
transformation of iris and periocular skin
color to dark because of the increasing
melanosomes in the melanosit cell. The
other side effects is hyperemic conjunctiva,
hypertricosis, trichiasis, districhiasis and
growing hair around the eyes, however this
side effect is reversible if the medication
stopped.
 blindness, periorbital dermatitis, sensitivity
reaction. In patient with primary open angle
PICTURE 4. The Chemical Formula of glaucoma or ocular hypertension, the
Latanoprost thickness of cornea usually increase with
dorzolamide.
(Cited from Glaucoma Medical Therapy
Principle and Management textbook, 2th
edition, by Peter AN. Oxford 2008. Page 34)
Picture.6 Dorzolamide chemical formula (
glaucoma medical therapy principle and
management, 2th edition, by peter AN.
PICTURE 5. Work mechanism of
Oxford 2008. Page 132)
Latanaprost
(Cited from Glaucoma Medical Therapy
Principle and Management textbook, 2th Picture.7 The Diagram of aquos humour
edition, by Peter AN. Oxford 2008. Page 35) production, in non-pigment ciliaric
processus epitel. Correlation between Na+,
K ATP-ase and carbonic anhydrate-link
Dorzolamide bicarbonate production

Dorzolamide first introduced in

America in 1998, that reduces intraocullar
Chapter III
pressure with reducing the production of
aquous humor. Dorzolamide inhibits the CONCEPTUAL FRAMEWORK AND
isoenzime carbonic anhydrate in ciliar body. HYPOTHESIS
The recommendation distribution is three
times a day. Reduced intraocular pressure
with this drugs is 14.7% up to 27% after a
two hours admission and 12.9% up to 17.6% Conceptual Framework
after an eight hours admission. The package
come in a 2% eyedrops and used in treating
glaucoma and oculi hypertension. The Research Hyphotesis
average reduced intraocular pressure is
estimated 4 to 6 mHg in its peak (2 hours 1. The administration of Latanoprost is
admission) and 3 to 4.5 mmHg (8 hours better than Dorzolamide in
admission) in a clinical trial. preventing the progression thinning
of the retina nerve fiberse with
Dorzolamide do not present base Normal Tension Glaucoma patients.
acid imbalance or electrolyte imbalance and
severe systemic side effects if compared
with CA inhibitor and not likely beta
adrenergic agonist, which contraindicated in
asthma disease or cardiac disease.
Topical carbonic anhydrate inhibitor
has minimal ocular reaction side effects,
such as irritation, bitterness, temporary
 Chapter IV
RESEARCH METHODOLOGY
The method of research
The research methods used in this
research is experimental comparative with
cross sectional approach. This research aims
to make differences between latanoprost and
dorzolamide against progression of RNFL
depletion on glaucoma normotensif patients.
Place and time of Research
a. Location of study
The location of study is Eyes
polyclinic at Prof. Kandou General
Hospital, Manado
b. Time of study
The research carried out on October
2012 until Mei 2013
Variables
The research using two variables
specifically independent variables the type
of therapy which is latanoprost and
drozolamide as well as dependent variables
which is the thinning of retinal nerve fibers.
Operational definition
1. Latanoprost is an analog esther
prostaglandin from alpha-2
prostaglandin with its function is to
decrease the intraocular pressure
while also on the other hand increase
uveoscleral outflow.
2. Dorzolamide hydroclodire is a first
line topical drop medication of
anhidrate-inhibitor and being used in
medical practices that works by
decreasing the intraocular pressure
with reducing the amount of aquous
humor.
3. The progresitivity of RNFL's
depletion marks the decreasing
process of RNFL gradually which
caused the early symptoms of
Glaucoma.
4. Normal Tension Glaucoma is a
disease marks by optical neuropathy
and related to the loss of visional
function with normal intra-ocular
pressure which is less than 12mmHg
& the front optical angle is opened.
5. OCT is a non-invasive tool, non-
contactable to detect the thickness of
RNFL.
Population and Sample
1. Population
The population of this study
include all the patients in Glaucoma
Department in Prof. DR. R.D
Kandou General Hospital of Manado
and had been diagnosed as an open
angle glaucoma through anamnesis,
Tonometry examination, Visual
field, Gonioscopy, and OCT.
2. Sample
The sample of this research
involved all open angle glaucoma
patients who visited Glaucoma clinic
in Prof. DR. R.D Kandou General
Hospital of Manado and meets the
inclusion and exclusion criteria,
including:
a. Inclusion criteria:
Open corner of the eyes
Cupping optic nerve
glaucomatous and neuroretinal rim
disappearance
Visual field defects and
glaucomatous papil
No secondary causes of optic
neuropathic glaucomatous
 Eyeball tension is from 10 to 21
mmHg
No contraindication of
latanoprost and dorzolamide
Clear refractive media
≥ 40 years of age
b. Exclusion criteria:
Patients experience the
contraindication of latanoprost
and dorzolamide utilization
3. Sample Size
This research used sample size
formulated by Kirk (1982), as presented
below:
2𝑘∅2
n=
𝐶2
Explanation:
n = sample size
k = total group (k=2)
Ø = provided value in table from Kirk’s
book, if α and power are known
C>0 determined by the researcher
If it uses k=2, α=0.01 and C=2, it will get
n=8 for each group
Research instrument
Instrument used is a form of
questionnaire which was given to the
respondents to be answered and OCT.
Questionnaire is divided into two section,
the first part of the question about the
identity of respondents consisting of age,
gender, education and employment. The
second part contains questions concerning
knowledge about glaucoma disease
Data collection Techniques
Data obtained directly from
respondents through interviews using
questionnaires and inspection so that the
diagnosis of open-angle glaucoma can be
determined. The stage of data collection as
follows:
1. Introduction as well as delivering the
goals and purpose of the research is
done to the respondent
2. Give a willingnesssheetto participate
in research as well as signed by the
respondent.
3. Do eye examination to the
respondents to diagnose open-angle
glaucoma (visual acuity examination,
intraocular pressure examination
with Goldmann tonometer, visual
field test with perimetry and RNFL
with OCT) .As for tools and material
that is required when eye
examinations are:
Snellen Chart
Slitlamp
Goldmann tonometer
Static Perimetry
OCT
Direct Opthalmoscope
Latanoprost
Dorzolamide
Tropicamide 0,5%
Goniolens
CMC Solution
4. evaluate the thickness of RNFL after
following 3 months using latonoprost
or dorzolamide
Statistic Analysis
The result of this research will be
analyzed using non-paired t-test to test the
hypothesis if the data of both group spread
normally, if not, mann whitney test is used
with the value of meaning is p<0,05.
Data statistics will use SPSS version 21.
 CHAPTER V Type of Age IOP CCT
Therapy Beginn End
ing
RESULT Latanoprost Total 4 4 4 4
Mean 54.75 10.5 9.87 547.12
This study was conducted at the Standard 7.89 0.96 0.79 0.82
Department of Ophthalmology RSU Prof. R. deviation
Dorzolamide Total 4 4 4 4
D. Kandou Manado for 10 months from Mean 56 11 9.69 547
March to December 2013 and continued Standard 10.16 0.82 0.53 2.65
with monitoring. deviation
IOP: Intraocular pressure
The aim of this study was to CCT: Central Corneal Thickness
determine the comparison of effectiveness
between latanoprost and dorzolamide in Trial Results
preventing the progressiveness of thickness
of retina nerve fiber layer through 16 eyes The results of latanoprost and
that compatible, which is divided into two dorzolamide therapy on the layer of retinal
groups, the first group using latanoprost and nerve fibers using optical coherence
the other using dorzolamide. tomography showed groups that use
latanoprost, average thickness of the interior
Subject Characteristics nerve fibers before therapy is 113 µm and
The distribution based on sex in the after therapy is 111 µm, average thickness
study (Table 1) was 7 male and 1 female of the superior nerve fibers before therapy is
(Table 3). 112.5 µm and after therapy is 107 µm,
whereas groups that use dorzolamide,
Table 3. Distribution based on sex average thickness of the interior nerve fibers
before therapy is 125.75 µm and after
Sex Kind of Therapy Total therapy is 125.38 µm, average thickness of
Latanoprost Dorolamide the superior nerve fibers before therapy is
Male 4 3 7 122.38 µm and after therapy is 121.38 µm.
Female 0 1 1 (table 5)
Total 4 4 8
Tabel 5. Distribution of inferior and
The distribution based on age, superior nervous fiber thickness
intraocular pressure and central corneal
thickness found that the average age that
using latanoprost was 54.75 years and 56 *tested with T test
years for dorzolamide, the average of
intraocular pressure that using lanataprost **tested with Mann-Whitney U test
was 10.5 mmHg and dorzolamide was 11
mmHg, and the average of central corneal Test result on Tabel 5 showed that;
thickness for using the latanoprost and
1. There was no significant Inferior
dorzolamide are each 547.12 µm and 547
difference before Latanoprost
µm (Table 4).
and Dorzolamide therapy (p=
Table 4. Patient distribution based on age, IOP 0,272 > α= 0,05)
and CCT 2. There was no significant Inferior
difference after Latanoprost and
 Dorzolamide therapy (p= 0,237 >
α= 0,05)
3. There was no significant
Superior difference before
Latanoprost and Dorzolamide
therapy (p= 0,834 >α= 0,05)
4. There was no significant
Superior difference after
Latanoprost and Dorzolamide
therapy (p= 0,713 >α= 0,05)
On the nasal and temporal retinal
nervous fibers thickness test, it was found
that the group that used latanoprost has an
average nasal nervous fibers thickness of
75,88 μm prior to therapy and 72,88 μm
after the therapy, the average temporal
nervous fibers thickness before therapy is
60,25 μm and 59,13 μm after the therapy.
While the group that used dorzolamide has
the average of nasal nervous fiber thickness
of 64,88 μm prior to therapy and 64,50 μm
after therapy. The average temporal nervous
fibers thickness before the therapy is 82,38
μm and 81,75 μm after therapy (Tabel 6).
Tabel 6. Distribution of nasal and
temporal nervous fiber thickness
*tested with T test
Test result on Tabel showed that;
1. There was no significant Nasal 1
difference between latanoprost
therapy and dorzolamide therapy (p=
0,074 > α= 0,05)
2. There was no significant Nasal 2
difference between latanoprost
therapy and dorzolamide therapy (p=
0,253 > α= 0,05)
3. There was a significant Temporal 1
difference between Latanoprost and
Dorzolamide therapy (p= 0,025<α=
0,05)
4. There was a significant temporal 2
difference between Latanoprost and
Dorzolamide therapy (p= 0,024 <α=
0,05)
Chapter VI
DISCUSSION
A study has been conducted on 16
samples whose eyes have been diagnosed as
having normotensive glaucoma according to
clinical examination, perimetry, gonioscopy,
funduscopy, OCT, and fulfills the inclusion
criteria. On the first visit, after diagnosis of
normotensive glaucoma was set, a quadrantt
plot retinal nervous fiber thickness
evaluation was done on the inferior,
superior, nasal, and temporal area. Two
groups were made and then each of the
group was given latanoprost or dorzolamide.
A retinal nervous fibers evaluation was
conducted three years after.
It was explained before that a
normotensive glaucoma is a condition where
patient has normal intraocular pressure but
has a glaucomatous papil signs that resemble
POAG. Intraocular pressure ranges from
10.5 to 11 mmHg and the average thickness
of central corneal layer is 547μm, a cribrosa
lamina defect, optic nerve cupping, a
migraine complain and periorbital pain
support the diagnosis. According to the
literatures it was mentioned that the central
corneal thickness of ±550 μm becomes one
of an important factor in assessing
normotensive glaucoma due to the thickness
that exceeds normal thickness, hence the
intraocular pressure tends to be higher, on
the contrary, if the thickness is less than
normal, the intraocular pressure tends to be
lower and causes a bias in the study. The
principle of glaucoma management still
refers to decrease of intraocular pressure,
even if the pressure is normal, because
according to literatures, around 30%
protection effect of visual field and retinal
nervous fibers status occurred on
normotensive glaucoma patients who had
anti glaucoma therapy, compared to those
who had never had therapy. The first line
drug of choice for open angle glaucoma is
Latanoprost and dorzolamide due to their
effectivity of reducing intraocular pressure
without a systemic adverse effect.5,7
Study result showed that a depletion
of retinal nervous fibers occurred after
therapy on the inferior and superior area,
especially toward the group that used
latanoprost for approximately 0,5-5 μm, but
was statistically insignificant between two
groups of medication (p= 0,237) on the
inferior and (p=0,713) on the superior, it
could be understood that the effect of both
medication was quite well in preventing
depletion of retinal nervous fibers. On
examination, nasal retinal nervous system
experienced approximately 1-3μm depletion
with p value 0,253, hence showed that there
was no significant depletion statistically for
each of the therapy, which explains that both
medication were quite effective in
preventing depletion of retinal nervous
fibers. On the other hand, the temporal layer
experienced significant depletion on the two
kinds of therapies, dorzolamide had a better
statistic effectivity (p= 0.024) compared to
latanoprost. Theoretically, it was explained
that one of the early signs of normotensive
glaucoma is a defect on retinal nervous
fibers, which precedes other symptoms such
as defect of visual field. However, in this
study, the RNFL defect was not too
significant on samples that have undergone
therapy for 3 months. The RNFL depletion
on glaucoma was aggravated by a high
intraocular pressure, vascular insufficiency
along with autoregulation disorder on optic
nerve. Although people with NTG has
normal intraocular pressure during the day,
but mostly they have a broad diurnal
variation, where the escalation at dawn or
night time can exceed 10 mmHg and has the
potential of damaging optic nerve albeit the
persistence was quite long and often time
unnoticed by the patient. That way, the goal
of NTG therapy is still by administering
antiglaucoma medication to decrease
intraocular pressure.
The effectiveness of both medication
in this study apparently have a value to
lowering the IOP and other symptoms such
as migraine, periorbital pain during research
time.
CHAPTER VII
CONCLUSION AND
RECOMMENDATIONS
Conclusion
Based on statistical tests, there was
no significant value found that latanoprost
was more effective than dorzolamide for the
progressive depletion of inferior, superior
and nasal retinal nerve fibers for both groups
of studies, but dorzolamide was more
significant than latanoprost for the depletion
of retinal temporal nerve fibers.
Recommendations
This study has some limitations
which is, patients who should be examined
the eyeball pressure after both of drugs
therapy, need to be examined and periodic
evaluation of the point of view with
humpreyperimetry more sensitive than
perimetry oculus easyfield. Since the
depletion of retinal nerve fibers in patients
with normotensive glaucoma is slow, this
study should be undertaken for a minimum
period of 6 months. As well as the
insignificant statistics test results, this study
needs to be continued.