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A Dissertation on
ANALYTICAL STUDY OF THE PREVALENCE AND RISK FACTORS
FOR ARMD IN A TERTIARY CARE CENTRE BY SCREENING
INDIVIDUALS ABOVE 60 YEARS
Dissertation submitted for
M.S.Degree in Ophthalmology
May 2018
THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY
CHENNAI, TAMILNADU
MAY - 2018
DECLARATION
I hereby declare that this dissertation entitled “ANALYTICAL
STUDY OF THE PREVALENCE AND RISK FACTORS FOR ARMD IN
A TERTIARY CARE CENTRE BYSCREENING INDIVIDUALS ABOVE
60 YEARS’’ is a bonafide and genuine research work carried out by me
under the guidance of Dr.M.Hemanandini. M.S.,D.O Associate Professor,
Department of Ophthalmology, Coimbatore Medical College & Hospital,
Coimbatore.
This is submitted to The Tamilnadu Dr.M.G.R. Medical University,
Chennai in partial fulfillment of regulations required for the M.S
Ophthalmology, Branch III Degree Examination to be held in May 2018.
Date:
Place: DR KOCHAMI.P.A
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation entitled “ANALYTICAL STUDY
OF THE PREVALENCE AND RISK FACTORS FOR ARMD IN A
TERTIARY CARE CENTRE BYSCREENING INDIVIDUALS ABOVE
60 YEARS” is a bonafide and research work done by Dr KOCHAMI P.A
Post Graduate in M.S. Ophthalmology under my direct guidance and
supervision to my satisfaction in partial fulfillment of the requirement
for the degree of Master of Surgery in Ophthalmology, Branch III .
Date: Guide
Department of ophthalmology
Date: HOD & PROFESSOR,
DEPT OF OPHTHALMOLOGY
Date: Dean,
Coimbatore Medical College & Hospital,
Coimbatore
ACKNOWLEDGEMENT
I express my gratitude to Dr.B.Asokan, M.S, MCh, the Dean,
Coimbatore Medical College Hospital for providing facilities to carry out my
project work successfully.
I sincerely thank Prof. Dr.S.Padmanabhan, Chief and HOD, Department of
Ophthalmology for his constant guidance and encouragement throughout the
period of my study.
I am grateful to Prof.Dr. M.HEMANANDINI M.S., D.O., Associate
Professor, Department of Ophthalmology for her constant guidance and
encouragement throughout the period of my study.
I owe my gratitude to my Assistant Professors Dr.J.Saravanan M.S.,
Dr.C.Jeevakala M.S., D.O., Dr.P.Sumathi M.S., Dr.K.Malligai D.O.DNB, Dr.P.
Mohanpriya M.S., Dr.K.Sathya M.S., Dr. Karthikeyan M.S., Dr. Haripriya
M.S., for helping and guiding me in completing this work.
Thanks to the administrators and nursing staff for having helped me
whole heartedly to complete this work.
Finally, I would like to thank all my patients for their immense and
patient cooperation.
Date:
Place: Dr.Kochami P.A.
ABBREVIATIONS
AMD - Age Related Macular Degeneration
RPE - Retinal Pigment Epithelium
VEGF - Vascular Endothelial Growth Factor
EDCCS - The Eye Disease Case Control Stud
HDL - High density lipoprotein
AREDS - The Age Related Eye Disease Study
ECM - Extracellular matrix
AGEs - Advanced-glycation end products
PED - Pigment Epithelial Defect
SD-OCT - Spectral Domain Optical Coherence Tomography
FFA - Fundus Fluorescein Angiography
ICGA - Indocyanine Green Angiography
OCT - Optical Coherence Tomography
PCV - Polypoidal Choroidal Vasculopathy
PDT - Photodynamic therapy
CNVM - Choroidal Neovascular Membranes
MPS - Macular Photocoagulation Study
BP - Blood pressure
DM - Diabetes mellitus
BMI - Body mass index
CAD - Coronary artery disease
INDEX TO TABLES
SL.NO TITLE Page No
1 Gender wise distribution in ARMD 53
2 Age wise distribution of ARMD 54
3 Age wise distribution of dry and wet ARMD 55
4 Chi Square- Age in ARMD 56
5 Distribution of Hypertension in ARMD 57
6 Distribution of Diabetes in ARMD 58
7 Distribution of Smoking in ARMD 59
8 Distribution of Alcoholism in ARMD 60
9 Distribution of Diet pattern in ARMD 61
10 Distribution of CAD in ARMD 62
11 Distribution of H/O cataract surgery in ARMD 63
12 Chi Square-Cataract surgery in ARMD 64
13 Distribution of Exposure to sunlight in ARMD 65
14 Distribution of BMI and Age of menopause in ARMD 66
15 Distribution of Soft drusen in ARMD 67
16 Distribution of Pigmentary abnormality in ARMD 68
17 Distribution of Dry and Wet ARMD 68
18 Distribution of Dry & Wet ARMD 70
INDEX TO CHARTS
SL.NO TITLE Page No
1 Sample distribution 52
2 Gender wise distribution in ARMD 53
3 Age wise distribution of ARMD 54
4 Distribution of Hypertension in Dry and Wet
ARMD
57
5 Distribution of Diabetes in Dry and Wet ARMD 58
6 Distribution of Smoking in Dry and Wet ARMD 59
7 Distribution of Alcoholism in Dry and Wet ARMD 60
8 Distribution of Diet pattern in Dry and Wet ARMD 61
9 Distribution of CAD in Dry and Wet ARMD 62
10 Distribution of H/O cataract surgery in Dry and Wet
ARMD
63
11 Distribution of Exposure to sunlight in Dry and Wet
ARMD
66
12 Distribution of different forms of ARMD 69
13 Distribution of Dry and Wet ARMD 70
INDEX TO FIGURES
SL.NO TITLE Page No
1 Fundus photo of right eye showing normal fundus 7
2 Photoreceptor-RPE-Bruch’s membrane 9
3 Fundus photo of left eye showing hard drusen 25
4 Fundus photo of right eye showing soft drusen 26
5 Fundus photo of right eye showing soft drusen with
pigmentary abnormality
29
6 Fundus photo of left eye showing Geographic atrophy 31
7 Fundus photo of left eye showing active CNVM 39
8 Fundus photo of right eye showing disciform scar 41
CONTENTS
S.NO TITLE PAGE NO
1. INTRODUCTION 1
2. REVIEW OF LITERATURE 3
3. AIM OF THE STUDY 48
4. MATERIALS AND METHODS 49
5. RESULTS AND OBSERVATIONS 51
6. DISCUSSION 71
7. SUMMARY 74
8. CONCLUSION 76
9. BIBLIOGRAPHY
ANNEXURES:
PROFORMA
KEY TO MASTER CHART
MASTER CHART
1
INTRODUCTION
Age related degeneration of the macula is a disease that blurs the
sharp central vision which adversely affects daily living activities like
reading,writing and driving ,and the affected individuals lose their
independence in their retirement life. It is a leading cause of irreversible
vision loss among people aged 60 or older. AMD is the main cause of
adult blindness in developed countries.AMD is commonly encountered in
Indian population also as it is in western countries.1,2With rapidly
growing older population, it has been estimated that, the geriatric
population will rise to over 1.2 billion by 2025, ~840 million of which
would be in the developing countries.3 With such a increase in the
geriatric population, it is expected that this problem may even reach
epidemic proportion in our society.
The early ARM which accounts about 85% of the cases includes
the presence of drusen and/or retinal pigment epithelium (RPE)
abnormalities for which no definite treatment is available. The late ARM
includes geographic atrophy of RPE or choroidal neovascular complex
accounts the remaining 15% cases. Without treatment, the late ARM will
rapidly deteriorate due to retinal destruction and subsequent scarring.
Evidences suggests that AMD is a multi-factorial disease but the full
2
aetiopathogenesis of AMD has not yet been unveiled. Studies from
western population suggests that lifestyle, nutritional, and genetic factors
are involved in the pathogenesis of AMD.4 Daily smoking is a strong risk
factor for the presence of late AMD. Increasing age and family history of
disease are consistently established as associated risk factors for late
AMD, neither of which can be modified. So refrain from cigarette
smoking is the only possible way to decrease the AMD incidence. The
National Eye Institute study, The Age-Related Eye Disease Study
(AREDS & AREDS 2) found that daily intake of certain minerals and
high-dose vitamins can slow progression of the disease in people who
have intermediate AMD, and those who have late AMD in one eye.
Treatment options for wet ARMD includes antiVEGF therapy, laser
photocoagulation and photodynamic therapy.5 The aims of this thesis
were to estimate the prevalence of AMD and examine the risk factors
associated with AMD.
3
ANATOMY
Retina or the nervous coat is the innermost layer of the eyeball. It is
thin , transparent layer with a purplish red color. Its thickness ranges from
0.56 mm near the optic disc to 0.1 mm at the ora serrata. It extends
anteriorly to become the epithelium of ciliary body and iris and
continuous posteriorly with the optic nerve. Its outer layer is in contact
with bruch’s membrane and inner surface is in contact with
vitreous.When seen through ophthalmoscope the parts of retina that can
be made out are
Optic disc
Peripheral retina
Macula
OPTIC DISC
Optic nerve leaves the retina at the optic disc. It is pale pink in
colour. It is much paler than surrounding retina as there is no vascular
choroid in the disc and nerve fibres behind the lamina cribrosa are
myelinated. Slightly depressed area at the centre of disc is cup where it is
pierced by central vessels of retina.
4
PERIPHERAL RETINA
MACULA
Oval yellowish area 5.5 mm at the posterior part of retina, 3 mm
lateral to optic disc. Yellow colour is due to presence of pigments-
xantophyll, lutein and zeaxanthin.
FOVEA CENTRALIS
1.5 mm depressed area at the centre of macula specialized for
colour vision and high spatial acuity. Area devoid of retinal blood vessels
within the fovea is foveal avascular zone (0.5 mm). Central pit within
fovea is foveola(0.35 mm). A small depression within foveola is umbo
(0.15mm). Parafoveal zone is area surrounding fovea,0.5 mm in width.
1.5 mm wide area surrounding parafoveal zone is perifoveal zone.
5
The 10 layers seen within the retina are:
1. Pigmented layer of retina
2. Layer of rods and cones
3. Outer limiting membrane of retina
4. Outer layer of nuclei
5. Plexiform layer – Outer
6. Inner layer of nuclei
7. Plexiform layer- Inner
8. Layer of ganglion cells
9. Layer of optic nerve fibres
10. Inner limiting membrane of retina
6
PIGMENTED LAYER OF RETINA
RPE extends from optic nerve margin to ora serrata as a single
layer of cells. The cells are tall narrow in the posterior pole and flatter
near the ora serrata. RPE cells are hexagonal in shape, its basal end rests
on a basement membrane and forms a part of choroids bruch’s
membrane. Apical end has numerous microvili that project between rod
and cones outer segment. Adjacent cells are bound together by zonula
adherens and the apical region by zonula occludens.
7
Fig : 1 Fundus photo of right eye showing normal fundus
8
RPE is highly metabolically active and has an important function
of outer segment renewal. The waste products from photoreceptors is
either recycled or degraded by the RPE and remaining is exocytosed to
choriocapillaries for clearance. RPE provides nutrients to the outer
segment of photoreceptors to maintain the visual function.
RPE forms the outer blood retinal barrier and prevents nonspecific
diffusion of materials from choroid. Melanosomes in RPE absorb the
excess light and protect retina from light damage. By aging metabolic
demand on each cell increases due to loss of RPE.6 To attain cytoplasmic
renewal RPE release cytoplasmic material into inner part of Bruch’s
membrane.7,8To handle outer segment renewal RPE has a catalytic
lysosomal system.9The end products called residual bodies fuses with
melanophores forming melanolipofuscin and it disappears by loss of
photoreceptor cells. With increasing age residual bodies containing
lipofuscin gets accumulated and leads to functional compromise of RPE.
9
Fig : 2 Photoreceptor-RPE-Bruch’s membrane
10
BRUCH’S MEMBRANE
Ultrastructurally Bruch’s membrane is penta-laminar
1. Basement membrane of RPE
2. Collagenous zone – inner
3. Elastic zone
4. Collagenous zone – outer
5. Basement membrane of endothelial cells of choriocapillaries
Heparan sulfate and chondroitin sulfate are seen in the interfiber
matrix of Bruch’s membrane. Any structural or compositional alteration
might affects its diffusion function and finally the RPE and outer retinal
function. As age increases the solubility of collagen decreases and results
in decreased permeability and less turnover of collagen. Due to cellular
distress of RPE long space collagen gets deposited in the Bruch’s
membrane.10With age fat and extraneous material gets deposited in the
Bruch’s membrane. Killingsworth et al states the various extraneous
material gets deposited as coated membrane bound (CMB) bodies and
their fragments as coated vesicle like (CVL) bodies.11
11
CHORIOCAPILLARIES
The capillary system of choroid vasculature lies just posterior to
Bruch’s membrane. They are arranged in a single layer in the inner
portion of choroid. At the posterior pole, the feeding arterioles and
draining venules enter the capillary plexus from below at right angles and
they are at same plane in equator and the posterior choroid. The vessel
wall is lined by fenestrated endothelium and its basement membrane
forms the posterior layer of the Bruch’s membrane.
Blaauwgeers et al stats that VEGF receptors 1 & 2 are expressed
on the retinal side of choriocapillaries.20From choriocapillaries RPE
transport nutrients to photoreceptors and the waste materials from
photoreceptors are recycled or degraded by RPE and the choriocapillaries
remove the exocytosed remaining waste from RPE. Blood flow in
choriocapillaries lacks autoregulation hence, any systemic hypoxia or
elevated intraocular pressure can cause decrease in choroidal PO2
.Decrease in choroidal perfusion can affect photoreceptor viability and
functioning and finally results in photoreceptor death.
12
AGE RELATED MACULAR DEGENERATION
AMD is the major cause of adult blindness in developed countries.
Some recent studies from India states that AMD is commonly
encountered in India as it is in the western countries.(21,22)As age is the
major risk factor, AMD is becoming more important in India undergoing
rapid increase in older population.AMD is a disease associated with
decline in central vision which is needed for daily activities like reading
and driving.AMD advances so slowly and causes no pain, so that people
won’t notice much change in their vision in the early stages. There are
two major types of AMD.
1) Exudative/Neovascular/Wet
2) Non exudative /Dry
PHOTORECEPTOR CHANGES IN AMD
Crucio et al observed that the photoreceptor loss in AMD
contributes to more severe loss of vision with disease. They also suggests
that photoreceptor loss occurs much before the disease process in RPE
and Bruch’s membrane.23
13
Dunaief et al observed the apoptosis of inner nuclear layer, RPE
and photoreceptors in AMD.24
Maeda et al states that loss of photoreceptors was directly related
to RPE loss, highlighting the importance of RPE in photoreceptor
viability.25
Photoreceptor loss in AMD is associated with scar formation and
thickness of scar was directly related to the degree of photoreceptor loss.
RPE CHANGES IN AMD
Age related changes in AMD were reduction in RPE cell density,
alteration in RPE pigmentation, reduction in melanosomes and increase in
number of lipofuscin granules. Hageman et al and Mullins et al suggested
that decrease in cell density was due to apoptosis due to accumulation of
toxic substances.26,27 After phagocytosis the reactive oxygen species
generated by light or oxygen metabolism fail to recognize by lysosomal
enzymes and leads to accumulation of lipofuscin. There by oxidative
stress of RPE will increase and contributes to pathogenesis of AMD.
Various cellular functions of RPE can be affected by change in
ECM, which mainly comes from Bruch’s membrane. Oxidative stress in
RPE can cause accumulation of advanced- glycation end products
(AGEs) in RPE and Bruch’s membrane. These AGEs also play an
14
important role in the induction of CNV, a characteristic of wet AMD. The
diffuse morphological changes at the level of RPE includes the basal
laminar deposits and basal linear deposits which are metabolic end
products from RPE and photoreceptors. RPE dysfunction cause
photoreceptor loss and in geographic atrophy photoreceptor and RPE
atrophy occurs in a horse shoe shaped manner around the fovea.
BRUCH’S MEMBRANE CHANGES IN AMD AND DRUSEN
FORMATION
With age three anatomical changes that occur in Bruch’s
membrane were accumulation of debris, lipid deposition and changes in
extracellular matrix. With increasing age the Bruch’s membrane becomes
thicker maximally in the inner collagenous layer followed by the outer
collagenous layer.
Guymer et al stated that the age related accumulation of
biomolecules which are the waste products of RPE metabolism results in
focal deposits and drusen formation.28Thickening of Bruch’s membrane
causes changes in hydraulic permeability and elasticity.
Hussain et al found that when compared to first decade in nineth
decade there is a 44% decrease in transport of dextrin through Bruch’s
membrane.29
15
Yuan et al reported increase in protein content of Bruch’s
membrane and the most elevated one is galectin 3. It is an advanced
glycosylation end product (AGE) receptor and its elevation is consistent
with the role of AGEs in dry AMD.30
The three morphological forms of sub RPE deposits are hard
drusens, soft drusens and basal deposits in or on the Bruch’s membrane.
Drusens are waste materials from RPE which cannot traverse Bruch’s
membrane for removal by the choriocapillaries.
Drusens in ARMD showed the presence of carboxyethyl pyrrole
and Gu et al suggested the use of carboxyethyl pyrrole antibodies as a
marker for ARMD.31
Hard drusens are less than 63µm , refractile sharp edged deposits
seen as yellow white lesions in fundus. This may be present in small
numbers without any consequence in aged eyes, but Bird et al describes
large number of hard exudates as independent risk factor for vision loss in
ARMD.32
Soft drusens are larger in size, fluffy appearance with indistinct
edges and shows a tendency to confluent with each other. Ambati et al
describes confluent drusens as independent risk factors for ARMD.33
16
Green et al describes basal linear deposits as independent and
specific risk factor for development of ARMD.34
CHOROID AND CHORIOCAPILLARIES IN ARMD
With age the thickness of choroid will decrease, density and
diameter of choriocapillaries and medium sized choroidal vessels will
decline resulting in decreased choroidal blood volume and blood flow
further leads to accumulation of waste materials in and at the Bruchs
membrane and formation of drusen.
In geographic atrophy the RPE and the photoreceptors degenerate
in a horse shoe shaped pattern surrounding the fovea and the loss of
choriocapillaries appears to be a secondary event suggesting that
geographic atrophy does not have a vascular etiology.
In wet ARMD loss of choriocapillaries results in ischemia of RPE and
RPE produces hypoxia induced angiogenic factors, leads to formation of
CNVM from choriocapillaries,venules and arterioles and grows through
the Bruchs membrane and spreads under the RPE.
17
RISK FACTORS
SOCIODEMOGRAPHIC RISK FACTORS
AGE
In all studies incidence, prevalence and progression of AMD increases
with age. According to Framingham Study risk of AMD increases 17
times on comparing oldest to youngest age group.35The Watermen study
states that every 10 years after 60 years the prevalence of moderate to
advanced AMD doubles.36
In the Beaver Dam Study early AMD is seen in 30% of
individuals more than 75 years and7.1% had late AMD ,in the remaining
23% developed early AMD in the next 5 years.37
GENDER
Various studies demonstrates that AMD is slightly more common
in women than in men. According to Beaver Dam Study, after the age of
75 early AMD and exudative AMD is more common in women than
men.38
The Blue Mountains Eye Study also shows a gender difference of higher
rates of AMD in women when compared to men.39
18
RACE
AMD changes were more common in whites than blacks. The
Baltimore Eye Survey states that AMD accounts for 30% of bilateral
blindness among whites but 0% among blacks.40
OCULAR RISK FACTORS
REFRACTIVE ERROR
Several studies showed association between AMD and hyperopia.
The Blue Mountains Eye Study suggests some association between early
AMD, but not with late AMD.41
IRIS COLOR
Light induced oxidative damage to retina can de decreased by
ocular melanin, which can acts as a free radical scavenger. Sandberg et al
found a decreased incidence of AMD in individuals with dark iris.42
CATARACT AND CATARACT SURGERY
The Beaver Dam Eye Study suggests an increased association
between AMD and nuclear sclerosis but not with cortical or posterior
subcapsular cataracts.43 Various studies states that cataract surgery
increases the risk of AMD because damaging ultraviolet lights can be
19
blocked by cataractous lens. Inflammatory reactions after cataract surgery
also causes the progression of early AMD to late AMD. 44
CUP-DISC RATIO
The EDCCS suggests a reduced risk of exudative AMD in eyes
with larger cup disc ratio.45
LIFESTYLE RISK FACTORS
SMOKING
Other than age the only consistently identified factor associated
with AMD is cigarette smoking.46In the Nurse’s Health Study AMD risk
increases with pack years of smoking showing a dose dependent
relationship.47Even after cessation of smoking risk for AMD remains
elevated for many years. Smoking increases the risk of macular
degeneration by
a) Decreasing HDL level
b) Increasing platelet aggregability and fibrinogen
c) Increasing oxidative stress and lipid peroxidation
d) Reduces the plasma levels of antioxidants
20
NUTRITIONAL FACTORS
ANTIOXIDANTS
Oxidative damage plays an important role in the development and
pathogenesis of AMD. Antioxidants can prevent oxidative damage to
retina which in turn prevent development of macular degeneration.
Vitamins like C, E and the carotenoids and trace minerals like zinc,
selenium, copper and manganese were involved in antioxidant functions
of retina.
In Age Related Eye Disease Study patients with no, early,
intermediate and advanced AMD were given a) Antioxidants b) Zinc c)
Antioxidants and Zinc and they were followed up for an average of 6.3
years. Results showed antioxidant and zinc combination is more effective
than individual supplements and has a protective effect against
development of advanced AMD.48
The Beaver Dam Study also states a protective effect of zinc
intake on early AMD.49Finally diet rich in antioxidants and increased
levels of carotenoids and antioxidant vitamins were associated with a
decreased risk of exudative AMD.
21
DIETARY FAT
A positive association exists between AMD and some type of
dietary fat.50The Eye Disease Case Control Study showed that increased
intake of certain types of fats such as vegetable monounsaturated and
polyunsaturated fats and linoleic acid were positively associated with late
AMD. Fish intake and diet rich in omega 3 fatty acids were protective in
subjects with low level of linoleic acid intake, a omega 6 fatty acid.51
The Beaver Dam Eye Study also showed a weak association
between early signs of AMD and high dietary fat intake, suggesting
certain cardiovascular risk factors are associated with AMD.52
ALCOHOL INTAKE
Studies related to alcohol intake and AMD gives mixed results. In
Beaver Dam Eye Study people who consumed beer in the past year
showed increased risk for RPE degeneration.53 The Blue Mountain Eye
Study showed a increased risk of AMD in current alcohol intakers.54
SUNLIGHT EXPOSURE
Various studies showed ARMD and sunlight exposure has minimal
or no association. The Beaver Dam Eye Study showed a increased risk
of late ARMD with increased leisure time spent outdoors in the
summer.55
22
The POLA Study reported a decreased incidence of soft drusen in
individuals wearing sunglasses regularly.56
OBESITY/ BODY MASS INDEX
Overweight and obesity had a positive association with risk of
AMD, and when compared with subjects in the normal range a significant
increased risk of late AMD was noted for obese individuals.
Qian-Yu Zhang et al states that in late stages of AMD the
association showed a dose dependent fashion indicating potential
protection may be conferred by keeping normal body weight and
avoiding further weight gain. 57
23
HYPERTENSION AND CARDIOVASCULAR DISEASES
The association between ARMD and cardiovascular diseases may
be due to common underlying atherosclerotic changes in cardiovascular
system and choroid vasculature. Hypertension affects the small arteries
and arterioles of sub macular region thus causing increased risk of
ARMD.
Hyman L et al suggested an increased risk of exudative AMD in
subjects with hypertension especially those taking antihypertensive
treatment. This study also showed a significant association between high
cholesterol intake and elevated serum HDL cholesterol and exudative
AMD.58
The Age Related Eye Disease Study (AREDS) found systemic
hypertension as a risk factor for the development of neovascular AMD
and large drusen.59
HORMONAL FACTORS
An increased prevalence of ARMD is seen in women who
reached early menopause. The Blue Mountains Eye Study reported a
significant decrease in early ARMD with increasing years between
menarche and menopause.60
The EDCCS showed a reduction of neovascular ARMD by 70% in
postmenopausal women who were on estrogen replacement therapy.61
24
GENETIC FACTORS
Evidences suggests that genetic factors play an important role in
the etiopathogenesis of AMD. Schmidt S et al suggested an association
of reduced risk of ARMD with ApoE4 allele.62
Mutations in ABCR gene, which is associated with Stargardt’s
disease has reported to seen in some cases of ARMD.63 Kimura K et al
suggested an association of manganese superoxide dismutase (MSD)
gene polymorphism and microsomal epoxide hydrolase exon-3 (MEHE-
3) with exudative ARMD.64
Ikeda T et al suggested paroxonase gene polymorphisms as
genetic risk factor for AMD.65
ARMD
Age related macular degeneration is the major cause of blindness in
people over 60 years of age. Among AMD 85-90% have dry type(
nonneovascular or nonexudative ) and 10-15% have wet type(
neovascular or exudative ). AMD usually starts as dry or nonneovascular
type and later may progress to geographic atrophy or wet form in one or
both eyes. If advanced AMD develops in one eye there is increased
chance of developing geographic atrophy or wet AMD in the fellow eye.
25
DRY (NONNEOVASCULAR OR NONEXUDATIVE ) AMD
Drusens are the typical lesions seen in dry AMD. Other features are
RPE abnormalities like atrophy or hyperpigmentation. Clinically drusens
are small round yellowish lesions seen at the level of RPE. They may
vary in size and shape and may have a crystalline appearance due to
calcification. Drusens are broadly classified into soft and hard types.
Fig : 3 Fundus photo of left eye showing hard drusen
26
Fig : 4 Fundus photo of right eye showing soft drusen
27
SOFT DRUSENS VS HARD DRUSENS
Hard drusen are round, yellow white lesions with size less than
63µm. They are commonly seen 80% of general population over 30 years
of age. They are not age related and doesn’t carry an increased risk for
development of neovascularisation. In contrast soft drusen are ill defined
with nondiscrete borders and size more than 63µm. Patients with large
(63 µm) ,soft or confluent drusen are more likely to have severe
manifestations of ARMD.66Drusens in the inner macula , area within
3000µm or 2 disc diameters are more significant.
FLUORESCENCE OF DRUSEN
Typically, small hard drusen hyperfluorescence early because of a
window defect where as large, soft or confluent drusen and drusenoid
PEDs slowly and homogenously stain late because of pooling of dye in
the sub PED compartment.
OCT OF DRUSEN
SD-OCT imaging of small and large drusen typically reveals sub-
RPE nodular elevations or even small RPE detachments with a notable
absence of intraretinal or subretinal fluid.
28
OUTCOME OF DRUSEN
Incidence of late AMD in patients with bilateral drusen depends mainly
on the degree of confluence of drusen within 1600µm of the centre of the
fovea. In patients with CNV in one eye, the presence of 5 or more drusen
and one or more large drusen were independently associated with
increased risk of developing wet ARMD in the other eye.67
ABNORMALITIES OF RPE
RPE abnormalities in dry AMD includes hyperpigmentation,
nongeographic atrophy and geographic atrophy. Increased
hyperpigmentation at the outer retinal level corresponds to
hyperpigmentation of RPE. On FA hyperpigmentation typically shows
blockage and on SD-OCT shows outer retinal hyperreflective foci.The
incidence of RPE hyperpigmentation increases with age and its presence
indicates greater risk of progression to advanced form of AMD.
Atrophy that doesn’t cover a contiguous area refers to
nongeographic atrophy. The affected retina appears pinker than normal
retina and FA shows diffuse hyperfluorescence not as bright as seen in
geographic atrophy.
29
Fig : 5 Fundus photo of right eye showing soft drusen with
pigmentary abnormality
30
GEOGRAPHIC ATROPHY
Geographic atrophy is the end result of dry form of AMD. It
presents as sharply delineated areas of atrophic patches, in which
choroidal vessels are more visible than surrounding areas. These patches
enlarge and coalesce and may be associated with a dense paracentral
scotoma. It usually expand in a horse-shoe like fashion around the fovea
or develops around the foveal perimeter in several areas
simultaneously.68Patients with geographic atrophy may demonstrate good
visual acuity until late in the course of disease as it spare fixation for
several years due to its characteristic spread which starts outside the rod
free area. Its determined by the manner in which lipofuscin accumulates
in the retina ( central rod free area has lower lipofuscin content) and the
distribution of macular pigment (lutein and zeaxanthin function as
antioxidants and protect macula from phototoxic damage).69 In most
cases geographic atrophy occurs in eyes with prominent drusen and
develops as the drusen regress and the distribution of drusen determines
the pattern of atrophy
Sadda et al reported a higher prevalence of reticular pseudodrusen
in patients with geographic atrophy and confers a hazard ratio of 4.9 for
progression to geographic atrophy.70
31
Biarnes et al states that It contributes to one third cases of late
AMD and leads to 20% cases of severe visual loss due to AMD.71
Fig : 6 Fundus photo of left eye showing Geographic atrophy
32
MANAGEMENT OF DRY AMD
Management of DRY AMD includes
Lifestyle modification
Vitamin supplements
Supportive measures in advanced stages
Lifestyle modifications include quitting smoking and alcohol
consumption, physical activity and reducing body mass index.72,73,74
The Blue Mountain Eye Study and the Alienor Study showed
that high intake of long-chain omega-3 polyunsaturated fatty acids
decreases the risk for AMD.75The role of dietary supplementation in dry
AMD was studied in detail in AREDS1 and AREDS 2.
33
AREDS
The Age Related Eye Disease Study was the prospective
randomized trials done by the National Eye Institute, to evaluate the
effect of high dose antioxidants on the progression of AMD.
AREDS 1 FORMULATION
Vitamin C – 500mg
Vitamin E – 400IU
Beta carotene – 15 mg
Zinc oxide – 80mg
Cupric oxide – 2 mg
This formulation reduces the risk of disease progression and visual
loss by 25% in patients with advanced AMD.76AREDS research found
that high dose zinc supplementation is associated with increased
incidence of genitourinary disorders and elevated intake of beta carotene
is associated with lung cancers.
34
AREDS 2
AREDS 2 was the multicentre randomized trial with primary goal
to determine the effect of addition of 10 mg lutein, 2 mg zeaxanthin and
1000 mg omega 3 long chain fatty acids to the AREDS 1 formulation
would reduce the disease progression to advanced AMD. AREDS 2 also
evaluated the effects of modifying AREDS 1 formula by reducing zinc
dosage and eliminating beta carotene.77
Crocetin(a natural carotenoid in saffron),curcumin and vitamin
B6,B9,B12 supplementation were also found to decrease the risk of
AMD.78,79,80
As many complement components and inflammatory mediators are
found in drusen, complement factor modulation may decrease their
activation and further immune mediated damage to the RPE.
Mones J et al showed intravitreal administration of an antibody
against complement factor D, lampalizumab decreases geographic
atrophy progression by 20.4% at 6 and 18 months with a good safety
profile.81
Anti complement component 5 and Fluocinolone acetonide were
under evaluation for intravitreal administration in geographic atrophy.
35
WET AMD ( NEO - VASCULAR/ EXUDATIVE )
Wet AMD is the more advanced form of age related macular
degeneration. It affects 10 -15 % of patients with AMD, but accounts for
90% severe visual loss caused by macular degeneration. Hallmark of wet
AMD is presence of choroidal noevascularisation(CNV). Associated
features includes RPE detachment, RPE tears, fibrovascular disciform
scarring and vitreous hemorrhage.82
Symptoms includes blurred vision and distortion, especially
distorted near vision, metamorphopsia, micropsia and scotoma.
Symptoms were due to subretinal or intraretinal fluid or RPE or
photoreceptor destruction by fibrous or fibrovascular tissue.83
CNV appear as grey green elevation deep to the retina with
overlying neurosensory retinal detachment. Presence of blood or lipid,
neurosensory retinal detachment, RPE folds below a shallow RPE
elevation indicates presence of CNV.
36
RETINAL PIGMENT EPITHELIAL DETACHMENT
Detachment of RPE from inner collagenous layer of Bruch’s
membrane, appear clinically as well demarcated dome shaped elevation
of RPE. Presence of neurosensory detachment overlying a PED gives a
clue to the presence of CNV. PED can be serous, fibrovascular, drusenoid
or hemorrhagic.
SEROUS PED
Orange dome shaped elevation with sharply deliniated edges with
pale margin of subretinal fluid. Associated subretinal fluid in irregular
pattern, choroidal folds, subretinal blood or lipids indicates presence of an
underlying CNV. FFA shows well demarcated area of hyperfluorescence,
notch in the well circumscribed area gives clue to underlying CNV.
ICGA shows oval area of hypofluorescence with faint ring of
hyperfluorescence.OCT shows Seperation of RPE from bruch membrane
by an optically empty area.
37
FIBROVASCULAR PED
PED caused by vessels and fibrous tissue infiltration is called
fibrovascular PED. FFA shows stippled hyperfluorescence with
persistence of staining and late leakage. OCT shows separation of RPE by
an optically denser area than in serous PED.
DRUSENOID PED
Shallow elevated pale areas with irregular scalloped edges formed
by a confluence of soft drusen, often located in the central
macula.84Drusenoid PED are associated with intermediate AMD, unlike
other types of PED which are generally associated with advanced
neovascular AMD.85FFA shows early diffuse hypofluorescence with
patchy relatively faint early hyperfluorescence to moderate irregular late
staining. ICGA shows predominantly hypofluorescence and homogenous
hyperreflectivity is seen in OCT.
HEMORRHAGIC PED
Elevated dark red dome shaped lesion with well defined outline
with underlying CNV or PCV.FFA shows dense masking of background
fluorescence.
PEDs are important markers of severity of disease, risk for progression,
and vision loss in AMD.
38
Pauleikhoff D et al stats that In advanced AMD, PEDs are seen
in up to 62% of eyes and in newly diagnosed PEDs 50% will experience
significant visual loss one year from diagnosis.86,87
Hoskin et al recognized RPE tear increasingly as a cause of
severe central visual loss in age related macular degeneration (AMD).88
CHOROIDAL NEOVASCULARISATION
Neovascular tissue associated with wet AMD described as
abnormal growth of blood vessel complex through bruchs from
choriocapillaries.
Any disturbances in bruchs
Break
Capillary buds to perforate outer aspect of bruch
Fibroblast acompany--fibrovascular complex
Disciform scarring
39
Fig : 7 Fundus photo of left eye showing active CNVM
CNVM is classified based on location relative to RPE
Type 1 CNVM seen beneath the RPE layer and appear as a fibrovascular
or hemorrhagic PED
Type 2 CNVM seen above the RPE layer and appear as lacy green-
grey lesions
40
Type 3 -new vessels from deep capillary plexus (RAP)
CNVM classified based on Fluorescein angiography findings
Classic CNVM appears above the RPE layer seen as bright lacy,
well defined early hyperflourescence increases in intensity and extend
beyond the early phase boundary.
Occult CNVM appears beneath the RPE layer, limits can be fully
defined and seen as a fibrovascular or hemorrhagic PED or Late leakage
from undetermined source.
Based on Location relative to the fovea:
Subfoveal (underneath the fovea)
Juxtafoveal (1-199 microns from the fovea)
Extrafoveal ( 200 – 1500 microns from the fovea)
In CNVM Indocyanine green angiography (ICGA) shows focal
hyperfluorescent
hot spot or plaque. It is very useful in the study of occult CNVM, and
helps in identifying the characteristic patterns of idiopathic polypoidal
choroidal vasculopathy (IPCV) and retinal angiomatous proliferation
(RAP). It is very important to correctly diagnose these disorders, since
they respond differently to treatment.
41
Fig : 8 Fundus photo of right eye showing disciform scar
42
AREDS CLASSIFICATION TO MONITOR PROGRESSION OF
AMD
CATEGORY DESCRIPTION
No AMD: none or a few small
drusen
Patients are essentially free of age‐
related macular abnormalities, with
a total drusen area less than five
small drusen and minimal
deterioration of visual acuity in
either eye
Early AMD: Patient will present
with any of multiple small drusen,
few intermediate drusen (63 to 124
μm in diameter), or RPE
abnormalities
Cases have these mild or
borderline, age related macular
features, still with little
change in visual acuity
Intermediate AMD: Individual will
have extensive intermediate drusen,
and at least one large drusen (125
μm) or geographic atrophy, not
affecting the fovea
The patient must not have advanced
AMD in both eyes, or at least have
one eye with visual acuity of 6/9 or
better
43
Advanced AMD: Geographical
atrophy affecting the fovea and or
or any of the features of
neovascular AMD
These patients have visual acuity of
6/9 or better and no advanced AMD
in one eye, whilst the other has
lesions of advanced AMD, or visual
acuity less than 20/32 with AMD
abnormalities sufficient to explain
reduced visual acuity
Wet macular degeneration presents with central visual blurring and
distortion. As AMD causes the central vision impairment, patients usually
have complaints such as difficulty with close‐work activities, straight
lines appearing wavy or distorted and dark patches in the central field of
vision.
An Amsler grid test is used to quantify the degree of visual
distortion and locate early visual problems of macular disease. It is done
by holding the grid 30 cm from the patients eye and ask to look at the
central dot and testing if they can see all four corners of the grid and if
any of the lines appears blurred ,wavy, bent or missing.
44
TREATMENT OF WET ARMD
Angiogenesis play an important role in the pathogenesis of wet
ARMD. So management of angiogenesis is vital in the treatment of wet
ARMD. The main angiogenesis regulators are VEGF, fibroblast growth
factor, pigment epithelium derived growth factor and extracellular matrix
molecules. Anti VEGFs are novel therapeutic agents that blocks VEGF A
and inhibits its biological activity and prevents formation of abnormal
blood vessels. Lucentis, or Ranibizumab, is an antibody fragment that
target all isoforms of VEGF A and licensed for use after MARINA and
ANCHOR studies.
In MARINA study the effect of monthly intravitreal ranibizumab
injection in patients with subfoveal, minimally classic or occult with no
classic CNV is compared with placebo controlled sham treatment. 95% of
study eyes experienced visual acuity improvement or stabilization
compared to 62% control eyes in 12 months. 40% had visual acuity
improvement of > 15 letters compared to control.
In ANCHOR study the effect of monthly intravitreal ranibizumab
injection in patients with predominantly classic subfoveal CNV is
compared with PDT with vertiporfin. 95% of ranibizumab treated eyes
45
maintained or improved vision at 12 months compared to 64% of PDT
treated eyes.
Pegaptanib sodium, is an RNA nucleotide aptamer that targets
only the VEGF isoform 165 responsible for pathological ocular
neovascularisation.
Avastin, or Bevacizumab is a recombinant humanised monoclonal
antibody against all isoforms of VEGF‐A is used off label in the
treatment of wet ARMD. The results of the CATT (Comparison of Age‐
Related Macular Degeneration Treatments Trials) study provided further
evidence for the efficacy of Bevacizumab in the treatment of neovascular
AMD.
Michels et al showed showing reduced retinal thickening and
improvement in visual acuity with the use of Bevacizumab in the
treatment of wet ARMD.89
The CATT (Comparison of Age‐Related Macular Degeneration
Treatments Trials) study provided evidence for the efficacy of
Bevacizumab in the treatment of wet ARMD. In this study at 1 year
Bevacizumab and Ranibizumab had equivalent effects on the visual
acuity when administered according to the same schedule.
46
PDT(Photodynamic therapy) is another treatment option for
treatment of wet ARMD.90 It is an outpatient procedure using a light
activated compound Vertiporfin (Visudyne). Inactivated form of drug is
injected as intravenous infusion at 6mg/kg over 10 mins, it travels and
accumulates in abnormal blood vessels under the centre of the macula.
Five minutes later drug is activated by diode laser for 83 seconds.
Activated drug releases energy and leads to formation of reactive oxygen
species and slows down the collection of fluid under the macula and
decreases the growth of scar tissue and abnormal membrane formation
under the macula.
Thermal laser photocoagulation with argon blue green laser is
another treatment option for wet ARMD. It is used for patients with
lesions outside the centre of the capillary free zone. The Macular
Photocoagulation Study (MPS) studied the effect of laser
photocoagulation in preventing severe vision loss in eyes with choroidal
neovascular membrane outside the fovea.91
Bressler et al compared the visual outcome following
submacular CNVM removal versus observation.92There was no
significant benefit for submacular surgery over observation.
47
Alternate surgical approach is macular translocation, where the
neurosensory retina of fovea in eye with recent onset subfoveal CNVM is
moved to a new location before permanent damage of retina.
Eandi et al concluded that there was not much benefit for
macular translocation surgery by accessing the functional outcome of
macular translocation for wet ARMD.93
48
AIM OF THE STUDY
AIM:
Screening for ARMD among individuals above 60 years at a tertiary care
centre and to estimate the prevalence of ARMD and examine risk factors
associated with ARMD.
49
MATERIALS AND METHODS
DESIGN OF THE STUDY
Analytical study of the prevalence and risk factors for ARMD in a tertiary
care centre by screening individuals above 60 years
STUDY SETTING
Study will be done at Department of Ophthalmology, Coimbatore
Medical College Hospital, Coimbatore.
STUDY PERIOD
One year period - from June 2016-May 2017
STUDY POPULATION
Patients attending Coimbatore medical college hospital will be included
in the study based on selection criteria. A minimum of 100 patients will
be included in the study.
Before commencing the study Ethics Committee approval was obtained
from Coimbatore Medical College Hospital, Coimbatore.
Inclusion criteria
1. Age>60 years
2. Both gender
50
Exclusion criteria
1. Patients with other retinal disorders like Angioid streaks,
pathological myopia.
2. Glaucoma patients
3. Patients who have undergone previous ocular surgeries.
4. History of Ocular trauma
STUDY METHODS
Consent is obtained from the patients selected for study.
Data collected using structured questionnaire addressing
life style habits and extent of smoking and alcohol use, socioeconomic
status, physical activity, and use of medication.
Clinical Examination includes
1. Uncorrected Visual Acuity ( UCVA)
2. Best Corrected Visual Acuity (BCVA)
3. Intra ocular pressure measurement by Non contact tonometer
4. Slit lamp examination
5. Fundus examination by direct,+ 90 D and Indirect Ophthalmoscopy,
Colour fundus, Red free fundus photo, Fluorescein angiogram
51
RESULTS
The collected data were analysed with IBM.SPSS statistics
software 23.0 Version.To describe about the data descriptive statistics
frequency analysis, percentage analysis were used for categorical
variables and the mean & S.D were used for continuous variables.To find
the significance in categorical data Chi-Square test and Fisher's Exact was
used. In both the above statistical tools the probability value .05 is
considered as significant level.
52
RESULTS AND OBSERVATION
Among the 1598 patients screened ARMD was found in 40 patients.
CHART 1: SAMPLE DISTRIBUTION
97%
3%
SAMPLE DISTRIBUTION
Negative Positive
Sample distribution
Negative 1558
Positive 40
53
Among the 40 ARMD patients 22 were females and 18 were males.
TABLE 1: GENDER WISE DISTRIBUTION IN ARMD
Sex Frequency Percent Valid Percent Cumulative Percent
Valid Male 18 45.0 45.0 45.0
Female 22 55.0 55.0 100.0
Total 40 100.0 100.0
CHART 2: GENDER WISE DISTRIBUTION IN ARMD
45%
55%
GENDER
Male Female
54
TABLE 2: AGE WISE DISTRIBUTION OF ARMD
Age range Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Upto 65
yrs
15 37.5 37.5 37.5
66 - 75
yrs
20 50.0 50.0 87.5
Above
75 yrs
5 12.5 12.5 100.0
Total 40 100.0 100.0
CHART 3: AGE WISE DISTRIBUTION OF ARMD
37%
50%
13%
AGE DISTRIBUTION
Upto 65 yrs 66 - 75 yrs Above 75 yrs
55
TABLE 3: AGE WISE DISTRIBUTION OF DRY AND WET ARMD
Crosstab
ARMD
Total DRY ARMD NV ARMD
Agerange Upto
65 yrs
Count 13 2 15
% within
ARMD
40.6% 25.0% 37.5%
66 - 75
yrs
Count 18 2 20
% within
ARMD
56.3% 25.0% 50.0%
Above
75 yrs
Count 1 4 5
% within
ARMD
3.1% 50.0% 12.5%
Total Count 32 8 40
% within
ARMD
100.0% 100.0% 100.0%
56
TABLE 4: Chi-Square Tests
AGE IN ARMD
Value df
Asymp. Sig.
(2-sided)
Pearson Chi-Square 12.917a 2 .002
Likelihood Ratio 10.245 2 .006
Linear-by-Linear
Association
5.571 1 .018
N of Valid Cases 40
ARMD was significantly associated with old age with p<0.05
57
TABLE 5: DISTRIBUTION OF HYPERTENSION IN ARMD
BP Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 27 67.5 67.5 67.5
No 13 32.5 32.5 100.0
Total 40 100.0 100.0
CHART 4: DISTRIBUTION OF HYPERTENSION IN DRY AND
WET ARMD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DRY ARMD NV ARMD
BP WITH ARMD
BP Non BP
58
TABLE 6: DISTRIBUTION OF DIABETES IN ARMD
DM Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 20 50.0 50.0 50.0
No 20 50.0 50.0 100.0
Total 40 100.0 100.0
CHART 5: DISTRIBUTION OF DIABETES IN DRY AND WET
ARMD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DRY ARMD NV ARMD
DM WITH ARMD
DM Non DM
59
TABLE 7: DISTRIBUTION OF SMOKING IN ARMD
Smoking Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 22 55.0 55.0 55.0
No 18 45.0 45.0 100.0
Total 40 100.0 100.0
CHART 6: DISTRIBUTION OF SMOKING IN DRY AND WET
ARMD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DRY ARMD NV ARMD
SMOKING WITH ARMD
Smokers Non Smokers
60
TABLE 8: DISTRIBUTION OF ALCOHOLISM IN ARMD
Alcoholism Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 13 32.5 32.5 32.5
No 27 67.5 67.5 100.0
Total 40 100.0 100.0
CHART 7: DISTRIBUTION OF ALCOHOLISM IN DRY AND
WET ARMD
0%10%20%30%40%50%60%70%80%90%
100%
DRY ARMD NV ARMD
ALCOHOL WITH ARMD
Alcoholic Non Alcoholic
61
TABLE 9: DISTRIBUTION OF DIET PATTERN IN ARMD
Diet Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Veg 14 35.0 35.0 35.0
Non
Veg
26 65.0 65.0 100.0
Total 40 100.0 100.0
CHART 8: DISTRIBUTION OF DIET PATTERN IN ARMD
35%
65%
DIET
Veg Non Veg
62
TABLE 10: DISTRIBUTION OF CAD IN ARMD
CAD Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 18 45.0 45.0 45.0
No 22 55.0 55.0 100.0
Total 40 100.0 100.0
CHART 9: DISTRIBUTION OF CAD IN DRY AND WET ARMD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DRY ARMD NV ARMD
CAD WITH ARMD
CAD Non CAD
63
TABLE 11: DISTRIBUTION OF H/O CATARACT SURGERY IN
ARMD
H/O
CATARACT
SX Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 24 60.0 60.0 60.0
No 16 40.0 40.0 100.0
Total 40 100.0 100.0
CHART 10: DISTRIBUTION OF H/O CATARACT SURGERY IN DRY AND WET ARMD
0%10%20%30%40%50%60%70%80%90%
100%
DRY ARMD NV ARMD
H/O CATARACT SX WITH ARMD
Cataract Non Cataract
64
TABLE 12: CROSSTAB -DISTRIBUTION OF H/O CATARACT
SURGERY IN ARMD
Crosstab
ARMD
Total
DRY
ARMD
NV
ARMD
H/O
CATARACT
SX
Yes Count 16 8 24
% within
ARMD
50.0% 100.0% 60.0%
No Count 16 0 16
% within
ARMD
50.0% 0.0% 40.0%
Total Count 32 8 40
% within
ARMD
100.0% 100.0% 100.0%
65
TABLE 13: CHI-SQUARE-DISTRIBUTION OF H/O CATARACT
SURGERY IN ARMD
Chi-Square
Tests Value Df
Asymp.
Sig. (2-
sided)
Exact Sig.
(2-sided)
Exact Sig. (1-
sided)
Pearson Chi-
Square
6.667a 1 .010
Continuity
Correctionb
4.746 1 .029
Likelihood
Ratio
9.480 1 .002
Fisher's
Exact Test
.013 .010
N of Valid
Cases
40
Cataract surgery showed a significant association with ARMD in our
study with p<0.05.
66
TABLE 14: DISTRIBUTION OF EXPOSURE TO SUNLIGHT IN
ARMD
EXPOSURE TO
SUNLIGHT Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Yes 20 50.0 50.0 50.0
No 20 50.0 50.0 100.0
Total 40 100.0 100.0
CHART 11: DISTRIBUTION OF EXPOSURE TO SUNLIGHT IN DRY AND WET ARMD
0%
20%
40%
60%
80%
100%
DRY ARMD NV ARMD
EXPOSURE TO SUNLIGHT WITH ARMD
Yes No
67
TABLE 15: DISTRIBUTION OF BMI AND AGE OF MENAPAUSE
IN ARMD
Descriptive
Statistics N Minimum Maximum Mean
Std.
Deviation
Age 40 60 85 68.50 6.397
BMI 40 19.6 29.6 23.008 2.2875
Age of
Menapause
22 40 50 46.91 2.562
Valid N
(listwise)
22
68
TABLE 16: DISTRIBUTION OF SOFT DRUSEN IN ARMD
SOFT DRUSEN Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Negative 8 20.0 20.0 20.0
Positive 32 80.0 80.0 100.0
Total 40 100.0 100.0
TABLE 17: DISTRIBUTION OF PIGMENTARY ABNORMALITY
IN ARMD
PIGMENTARY
ABNORMALITY Frequency Percent
Valid
Percent
Cumulative
Percent
Valid Negative 27 67.5 67.5 67.5
Positive 13 32.5 32.5 100.0
Total 40 100.0 100.0
69
CHART : 12 Distribution of different forms of ARMD
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
HARD DRUSEN
SOFT DRUSEN
PIGMENTARY ABNORMALITY
GEOGRAPHIC ATROPHY
Negative Positive
70
TABLE 18: DISTRIBUTION OF DRY AND WET ARMD
ARMD Frequency Percent
Valid
Percent
Cumulative
Percent
Valid DRY
ARMD
32 80.0 80.0 80.0
WET
ARMD
8 20.0 20.0 100.0
Total 40 100.0 100.0
CHART 13: DISTRIBUTION OF DRY AND WET ARMD
80%
20%
ARMD
DRY ARMD NV ARMD
71
DISCUSSION
During the study period, 1598 persons of 60 years and above
attended our OPD were screened for ARMD. On examination, 40 persons
were found to have ARMD and were included in this study.
The proportion of dry, wet and total ARMD based on population
screened during the study period were 2.0%, 0.5% and 2.5% respectively.
Soft drusen were found in 32 persons and 13 persons had retinal pigment
epithelial abnormality.
Among the persons with late ARMD, dry type was noted in 5
persons (38.4%) and 8 persons had neovascularisation (61.5%).
ARMD was bilateral in 28 persons (70%) and unilateral in 12
persons (30%).
In this study, out of 40 ARMD patients 22 (55%) were females and
18 (45%) were males. Females showed higher risk for ARMD which is
supported by Beaver Dam Study and Blue Mountains Eye Study.
15 persons (37.5%) were in 60-65 years range, 20 persons (50%)
were in 66-75 years range and 5 persons (12.5%) were more than 75
years of age. ARMD was significantly associated with old age with
72
p<0.05 which is supported by Framingham Study and Beaver Dam
Study.
Based on best corrected visual acuity for distance in better eye
one person (2.5%) had vision <3/60, 7 persons (17.5%) had vision 6/60-
3/60, 28 persons (70%) had vision 6/18-6/60 and 4 persons (10%) had
vision >6/18.
Analysing the risk factors, 27 persons (67.5%) were
hypertensive and 20 persons (50%) were diabetics. We couldn’t found
any significant relationship between hypertension or diabetes with
ARMD.
22 persons (55%) were smokers, and even though it’s the only
consistently identified risk factor for ARMD other than old age, we
couldn’t found any significant association between smoking and ARMD.
13 persons (32.5%) were alcoholics and 26 persons (65%) were
taking non vegetarian diet. We did not find any significant association
between alcoholism or diet habit with ARMD.
24 persons (60%) gave history of coronary artery diseases.
In this study, 24 persons (60%) had undergone cataract surgery
and 20 persons (50%) gave history of exposure to sunlight. Cataract
73
surgery showed a significant association with ARMD in our study with
p<0.05 and it was supported by Chew et al.
In this study BMI ranges between 19.6 and 29.6 with a mean of
23.008 and age of menopause ranges between 40 and 50 with a mean of
46.91. We could not find any significant association between BMI and
age of menopause with ARMD.
74
SUMMARY
This study entitled “Analytical study of the prevalence and
risk factors for ARMD in a tertiary care centre by screening individuals
above 60 years” is a hospital based analytical study.
The aim of the study was screening for ARMD among individuals
above 60 years at a tertiary care centre and to estimate the prevalence of
ARMD and examine risk factors associated with ARMD.
Analysing the risk factors and by modifying those risk factors in
ARMD patients would reduce the disease progression to advanced AMD.
A total of 1598 persons were screened and 40 persons were found to
have ARMD. Prevalence of total ARMD was found to be 2.5% based on
population screened during the study period.
Among total ARMD patients the magnitude of dry ARMD was
found to be more than wet form of ARMD.
Females had a high risk for ARMD than males in our study and
its consistent with various studies demonstrating ARMD is more common
in females than in men.
The overall age distribution ranges from 60-85 years with a mean of
68.5 and its significantly associated with ARMD with p<0.05.
75
Even though majority of ARMD patients were hypertensive and
smokers we could not found any association between them.
Some studies showed significant association between ARMD and
diabetes mellitus, but such association was not seen in our study.
Alcoholism and Coronary artery diseases were associated with ARMD
in some studies, but our study could not find a significant association.
Our study did not find any significant association between diet and
sunlight exposure with ARMD.
Our study also found a positive association between ARMD and cataract
surgery which is significant with p<0.05.
Among the ARMD patients, BMI ranges between 19.6 and 29.6 and
age of menopause ranges between 40 and 50 in females. These factors
were not significantly associated with ARMD in our study.
76
CONCLUSION
In the coming years, ARMD will become an important cause
of vision loss in India due to ageing population because of better
longevity.
Globally ARMD accounts for 9% of vision loss and it is usually
underestimated as it has no overt symptoms in the early stages. So
screening of individuals over 60 years is important to diagnose ARMD at
an early stage.
Screening and follow up for early diagnosis and progression
helps to initiate treatment at proper time in wet forms of ARMD.
By proper screening, we can also maintain the functional vision
and thereby improve the quality of life of patients.
Lifestyle modifications like avoiding smoking and alcohol
consumption, physical activity to reduce body mass index may help to
slow down the disease progression in some patients.
By placing the patients on diet rich in antioxidants, with increased
levels of carotenoids and vitamins can decrease risk of exudative ARMD,
which would reduce the disease progression to advanced ARMD.
77
Older age and cataract surgery have a definite association in the
progression of ARMD (p<0.05). Hence it is mandatory to rule out early
ARMD in patients undergoing cataract surgery.
Patients with early ARMD should also be explained about the
possibility of disease progression after cataract surgery, so that they can
be followed up and treatment can be initiated at appropriate time.
Hypertension, diabetes, smoking, alcoholism, CAD, BMI, age of
menopause or exposure to sunlight seems to play a role in the progression
of ARMD. Hence adequate control of comorbid conditions and cessation
of smoking and alcohol, can help to slow down the disease progression to
some extent.
Addressing the risk factors and regular eye examination can not
only reduce permanent vision loss but also preserves the residual
functional vision with the help of low vision care.
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population of Southern India: The Aravind Comprehensive Eye Study. Arch
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PROFORMA
NAME:
AGE: SEX: ADDRESS:
OCCUPATION:
BMI:
BP:
HISTORY OF SMOKING: YES/NO
HISTORY OF ALCOHOL INTAKE: YES/NO
DIETARY HABITS: VEG/NONVEG
HISTORY OF CARDIOVASCULAR DISEASES: YES/NO
HISTORY OF STROKE: YES/NO
AGE OF MENOPAUSE:
RE LE
1.Uncorrected visual acuity(UCVA) :
2.Refraction :SPH
CYL
AXIS
3.Best corrected visual acuity(BCVA):
4.Tonometry-Non contact tonometry:
5.Slit Lamp Examination :
Lids :
Conjunctiva :
Cornea :
Anterior chamber :
Iris :
Pupil :
Lens :
6.Fundus examination
Direct Ophthalmoscopy , +90 D and Indirect Ophthalmoscopy
RIGHT EYE LEFT EYE
7.In patients suspected of having fundus changes
RE LE
Fundus Fluorescein Angiography
CONSENT FORM
I Dr. KOCHAMI.P.A, is carrying out a study on the topic,
“ANALYTICAL STUDY OF THE PREVALENCE AND RISK FACTORS
FOR ARMD IN A TERTIARY CARE CENTRE BY SCREENING
INDIVIDUALS ABOVE 60 YEARS”
My research project guide is Dr.M.Hemanandini M.S.,D.O.
My research project is being carried out in the department of
Ophthalmology, Coimbatore Medical College Hospital, Coimbatore.
RESEARCH BEING DONE:
Screening for ARMD among individuals above 60 years at a tertiary care centre
and to estimate the prevalence of ARMD and examine risk factors associated
with ARMD.
PURPOSE OF RESEARCH
1. To estimate the prevalence of ARMD
2. To identify the risk factors associated with ARMD.
You, Shri./ Smt./ Kum. _________________________, aged ____ years, S/o
/ D/o / W/o ___________________________, residing at ____________
___________________________ are requested to be a participant in the
research study titled ‘ANALYTICAL STUDY OF THE PREVALENCE
AND RISK FACTORS FOR ARMD IN A TERTIARY CARE CENTRE
BY SCREENING INDIVIDUALS ABOVE 60 YEARS’ in Government
Medical College Hospital, Coimbatore. You satisfy eligibility criteria as
per the inclusion criteria. You can ask any questions or seek any
clarifications on the study that you may have before agreeing to
participate.
DECLINE FROM PARTICIPATION
You are hereby made aware that participation in this study is purely
voluntary and honorary and that you have the option and the right to
decline from participation in the study.
PRIVACY AND CONFIDENTIALITY
You are hereby assured about your privacy. Privacy of subject will be
respected and any information about you or provided by you during the
study will be kept strictly confidential.
AUTHORIZATION TO PUBLISH RESULTS
Results of the study may be published for scientific purposes and/or
presented to scientific groups, however you will not be identified; neither
will your privacy be breached.
STATEMENT OF CONSENT
I, , do hereby volunteer and consent to participate in
this study being conducted by Dr KOCHAMI.P.A .I have read and
understood the consent form / or it has been read and explained to me in
my own language. The study has been fully explained to me , and I may
ask questions at any time.
Signature / Left thumb impression of the volunteer
Date:
Place :
Signature and name of witness
Date:
Place :
Signature of the Investigator:
Name of the Investigator:
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KEY TO MASTER CHART
M-1 - Male
F-1 - Female
YRS - Years
BP - Blood pressure
DM - Diabetes mellitus
CAD - Coronary artery disease
BMI - Body mass index
NVARMD - Neovascular age related macular degeneration
Veg - Vegeterian
Non veg - Non vegeterian
Sl Number Name AGE
(YRS)
SEX IP/OP
Number
Vision BP DM Smoker Alcohol Diet CAD
BMI Age of Menapause
H/O CATARACT SX EXPOSURE TOSUNLIGHT HARD
DRUSEN SOFT
DRUSEN PIGMENTARY
ABNORMALITY GEOGRAPHIC
ATROPHY NV
AMD ( M -1 / F - 2 ) RE LE Y - 1 ,
N - 2 Y - 1 , N - 2
Y - 1 , N - 2
Y - 1 , N -2
Veg-1 , Non VEG- 2
Y-1 , N-2 Y-1 , N-2 Y-1 N-2
1 Rajendran 68 1 13612 6/24 6/9 1 2 1 1 2 1 23.1 - 2 1 + + - - - 2 Bakiyam 67 2 2658 6/18 6/18 1 1 2 2 1 2 23.6 50 2 2 + + - - - 3 subathal 65 2 12542 1/60 6/36 1 1 1 2 1 1 29.6 48 1 1 - - - - + 4 Ramasamy 68 1 3567 3/60 1/60 1 2 1 2 2 2 23.9 - 1 1 - - - - + 5 Damodaran 67 1 2345 6/24 6/18 1 2 1 2 1 2 24.0 - 2 2 + + - - - 6 Nagamma 80 2 26431 6/18 6/12 2 2 2 2 2 1 28.4 47 1 1 + + - - - 7 Thrisa 78 2 5632 1/60 6/36 1 1 2 2 2 1 24.5 49 1 2 + + + - + 8 Subramani 61 1 28764 2/60 6/24 2 1 1 1 1 2 21.7 - 1 2 - + + + - 9 Subbamma 65 2 8752 6/18 6/12 2 2 2 2 2 2 22.0 46 1 2 + + - - -
10 Sundari 85 2 4562 2/60 5/60 1 1 1 1 2 2 24.6 43 1 2 - + + - + 11 Gurusami 65 1 7652 4/60 3/60 2 2 1 1 2 1 22.4 - 1 1 - - - - + 12 Thirumalaisamy 65 1 8932 6/36 6/36 2 1 1 1 2 2 21.7 - 2 1 - + + - - 13 Muthayya 62 1 13781 4/60 6/60 1 1 1 1 2 1 25.0 - 1 1 - - - + - 14 Madheena 70 2 14562 2/60 3/60 1 1 2 2 2 1 21.4 45 2 2 - - + + - 15 Thangammal 70 2 9832 6/18 1/60 1 2 2 2 2 2 23.2 48 1 2 - - - - + 16 Perumal 71 1 10981 6/24 6/60 2 2 2 2 2 1 20.8 - 1 1 - + + - - 17 Mohini 55 2 11562 6/24 2/60 1 2 1 1 1 1 22.6 47 2 1 - + + + - 18 Kuppammal 75 2 15321 6/18 6/18 2 2 2 2 2 2 20.0 50 2 1 + + - - - 19 Lakshmi 67 2 7623 6/24 6/18 1 2 2 2 2 1 20.8 44 1 2 + + - - - 20 Saraswathi 65 2 9832 6/36 6/60 1 1 2 2 2 1 21.8 47 2 1 - + + + - 21 Kalimuthu 60 1 12612 6/36 6/36 1 2 1 1 1 2 23.4 - 2 1 -- + - - - 22 karuppan 75 1 14521 6/18 6/18 1 2 1 1 1 2 22.0 - 1 2 + + - - - 23 Muthu 70 1 17325 6/60 6/18 2 2 1 1 2 1 23.8 - 1 2 - + - - - 24 seethayammal 62 2 18521 6/60 6/36 1 1 2 2 2 2 24.6 48 1 2 - + + - - 25 shara 74 2 9945 6/24 6/60 1 2 2 2 1 1 28.2 49 2 2 - + - - - 26 Petchai ammal 79 2 5499 4/60 2/60 2 1 1 2 2 2 25.2 50 1 2 - - - - + 27 Ramathal 73 2 18437 6/36 6/18 2 2 2 2 2 2 22.4 40 2 1 - + - - - 28 Veerammal 67 2 19834 6/12 6/12 1 1 2 2 2 1 21.6 46 1 2 - + - - - 29 Selvam 60 1 21711 4/60 2/60 1 1 1 2 2 1 20.2 - 2 1 - + + - - 30 Pitchai 65 1 22761 6/36 6/36 1 1 1 1 2 2 20.6 - 2 1 - + + - - 31 Selvaraj 75 1 24652 6/18 6/18 1 2 1 2 1 1 21.6 - 1 2 - + - - - 32 Murugan 68 1 23498 6/18 6/36 2 1 1 2 1 2 19.6 - 2 2 - + - - - 33 Patiyammal 60 2 8965 1/60 1/60 2 2 1 2 2 2 24.8 44 2 1 - + - - - 34 Jayaraj 62 1 10898 6/18 6/18 1 2 1 1 1 2 21.9 - 1 1 + + - - - 35 Radha 65 2 10654 6/36 6/36 1 1 2 2 2 2 21.7 47 1 2 + + - - - 36 Kamaraj 68 1 16509 6/18 6/36 1 1 1 2 1 2 20.8 - 2 1 - + + - - 37 Sivagami 74 2 17902 6/60 6/36 1 1 2 2 2 2 23.6 46 1 2 + + - - - 38 Eswari 78 2 18900 1/60 6/60 1 2 1 2 1 1 26.2 48 1 2 - - - - + 39 Mani 67 1 26456 6/36 6/12 2 1 2 1 2 1 22.2 - 1 1 + + + - - 40 Ramathal 69 2 27888 6/24 6/36 1 1 2 2 1 2 20.8 50 1 1 + + - - -