Dry age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 65. It is characterized by the breakdown and loss of cells in the macula due to aging and can be categorized as either dry or wet AMD. Dry AMD accounts for 90% of cases and results in gradual vision loss over time due to buildup of drusen and development of geographic atrophy in the macula. Diagnosis is based on the presence of soft or large drusen, pigmentary abnormalities, and atrophy seen on examination and imaging like OCT. There is no cure for dry AMD and vision loss progresses slowly, resulting in central blind spots.

1. Dry Age related Macular
Degeneration
DR SHRUTI LADDHA

2. Introduction :
• ARMD: Defined as the loss of macular function
because of the degenerative changes of ageing.
• It is the leading cause of irreversible vision loss
and blindness in people aged > 65 years.
• It was responsible for 8.7% of all blindness
worldwide in 2007, and this figure is expected to
double by 2020.
• ARMD was found to be second cause of severe
visual loss after cataract.

3. AMD: TERMINOLOGY
• Referred as senile macular degeneration, a name
given by Haab as early as 1885.
• Age-related macular degeneration has recently been
named by Professor A C Bird and coworkers who
performed the International ARM Epidemiological study
group.
• The disorder is either referred to age related
maculopathy (ARM) or age-related macular
degeneration (AMD).

4. • The UN estimates the number of people with
AMD are about 20-25 million worldwide.
• WHO’s estimate is 8 million people with severe
visual impairment.
• Prevalence of AMD in >75 year age group varies
from 1.2% to 29.3% in different.
AMD: PREVALANCE

5. AMD: PREVALANCE
• 3 population based studies; the Beaver Dam Eye Study,
Blue Mountain Eye Study and the Rotterdam study
report the over- all prevalence rates to be 1.7% in US,
1.4% in Australia and 1.2% in Netherlands respectively.
• In South India, the prevalence is 1.1% whereas, another
study from North India reports the prevalence rate to be
4.7%.

6. POSTULATED RISK FACTORS:
• Ageing
– The Framingham Eye study (1976) showed the
prevalence
– 65-74 years- 11%
– 75-85 years- 28%
• Gender
– Blue Mountains study (2002) suggests that 5- year
incidence of neovascular AMD among women is double
that of men.
• Smoking
– The Beaver Dam Study (1992) disclosed a
relationship between the development of exudative
lesions and a history of smoking

7. POSTULATED RISK FACTORS:
• Cardiovascular Risk factors
– Hypertension: Rotterdam study (2003) suggests
positive correlation between high blood
pressure and increased incidence of AMD.
• Light
– Initially postulated hypothesis: UV-damage by
photo-oxidative damage via reactive oxygen
intermediates.
– The Blue Mountains Eye Study (2002) disclosed
no relationship between light and AMD.

8. POSTULATED RISK FACTORS:
• Nutrition
– Several studies (including AREDS)
have described the beneficial
effects of dietary carotenoids,
anti-oxidants, Zn and omega-3
fatty acid in slowing the course of
the disease.
• Exogenous Post Menopausal
Oestrogen
– The use of exogenous
supplements in post

9. GENETICS
• Family history of macular degeneration:
– Autosomal dominant with variable penetration
– In first degree relative with macular
degeneration, chances is about 2.5 times.
• Macular Degeneration Gene:
– Few studies have described the increased risk of AMD
associated with polymorphisms of complement factor
H (HF1/CFH)
– single nucleotide polymorphisms on 1q32, 6p21, and
10q26 are the risk for development of AMD

10. RETINAL PIGMENT EPITHELIUM
The retinal pigment epithelium
(RPE) is a single layer of
hexagonally shaped cells &
attached to the photoreceptor
layer.
Functions -
• Maintain the
photoreceptors
• Absorption of stray (noise )light
• Formation of the outer blood
retinal barrier
• Phagocytosis and
regeneration of visual
pigment

11. • Each RPE cell is responsible for a diurnal cycle of engulfing
photoreceptor outer segments that have been shed
• The rod outer segments being digested by day and the cone
outer segments by night
• After phagocytosis –RPE lysosomes degrade the
photoreceptor outer segment

12. • In ARMD -After phagocytosis by the aged RPE, the lysosomal
degradation enzymes may fail to “recognize” these abnormal
molecules, causing molecular degradation to fail with
accumulation of lipofuscin in the RPE lysosomes.
• The normal, young RPE is composed of a single layer of
hexagonal cells of equal size and degree of pigmentation.
• With age-plemorphism

13. • Bruch’s membrane separates the RPE from vascular
choroid.
• Bruch’s membrane is composed of an inner and outer
collagenous zone (ICZ and OCZ) separated by an elastic
layer (EL).
• Linear relation exist between the age and thickness of
Bruchs membrane.
• Function of Bruch’s membrane is to provide
support to the retina.
• Choroid capillaries are a layer of fine blood vessels that
nourishes the retina and provides O2.

14. • Young
• Old
• Early AMD
• Advanced AMD

15. TYPES

16. DRY AMD
• Accounts for about 90% of all cases
• Also called atrophic, non-exudative or drusenoid macular
degeneration
• Clinically , dry AMD may manifest-
• Stage of drusen and/or hyperpigmentation
• Stage of incipient atrophy (non geographic
Atrophy)
• Stage of geographic atrophy

17. DRY AMD
D rusen

18. Insufficient oxygen and nutrients damages
photoreceptor molecules
With ageing, the ability of RPE cells to digest these molecules
decreases
Excessive accumulation of residual metabolic debris and hyaline
material (drusen)
Further disruption of RPE/photoreceptor metabolism
Cause variable amount of depigmentation and
eventually atrophy of overlying RPE
RPE membrane and cells degenerate and atrophy sets in
and central vision is lost

19. • Drusen:
• Drusen are aggregation of hyaline material located
between Bruch’s membrane and RPE.
• Drusen are composed of metabolic waste products from
photoreceptors.
• Hypo/hyper pigmentation of RPE may be present.

20. • Types:
– Small: <63 µ
– Intermediate: 63-124 µ
– Large: >125 µ
– Hard:
• generally small (<63 µ), bright yellow, solid appearing
drusen with well defined margins
• may be asymptomatic
– Soft:
• larger (>63 µ), pale yellow, ill defined, fluffy margins
• High risk for neovascular AMD

21. • Soft Drusen:
– Membranous:
• 63-175 µ
• Pale, shallow appearing drusen
– Granular:
• About 250 µ
• Solid appearing drusen
– Serous:
• >500 µ
• Have pooled serous fluid
• blister like appearance
• May result in serous PED

22. HISTOPATHOLOGY
y neo-vascular AMD.
• Drusen appear as focal areas of the eosinophilic material
between the basement membrane of RPE & BM.
• Deposits on the internal side of RPE basement membrane
called –basal laminar deposits & on its external aspects called
– basal linear deposits.
• Basal linear deposits are believed to form soft drusen
with the passage of time
Drusen

23. • Diagnostic criteria
• Degenerative disorder in persons >50 years,
characterized by the presence of any of the
following:
– Soft drusen (>63 µ)
– RPE abnormalities- areas of
hypo/hyperpigmentation (excluding pigment
surrounding small, hard drusen)
– Visual acuity (VA) is not a criterion for the
diagnosis

24. RPE degeneration, seen as:
• Focal areas of hypo- and hyper- pigmentation (‘stippling’)
• Associated with progression to late AMD with Visual loss
• Eventually areas of atrophy of the RPE revealing underlying
large & deep choriodal vessels
• ‘Geographic atrophy’ = end stage or Late advanced stage
of Dry AMD

25. DRY AMD

26. • Symptoms:-
Gradual mild to moderate impairment over months or years Both
eyes usually affected but often asymmetrically
Vision may fluctuate, & is often better in bright light
• Signs:-
Intermediate-large soft drusen may confluent Focal
hyper &/or hypopigmentation of RPE
Slow/progressive atrophy of RPE and photoreceptors
Drusenoid RPE detachment
Advanced form = Geographic Atrophy

27. Geographic Atrophy (GA)
• Clinical Features:-
•Signs/Symptoms:-
Marked decrease VA (unless foveal sparing)
Central field loss (positive scotoma)
Difficulty recognizing faces
Difficulty reading if large scotoma
Difficulty in dim light/adapting
Soft drusen present in early stages (significant risk factor for GA – due to
RPE detachment)
Decreased retinal thickness and increased visualisation of choroidal
vessels
Sharply demarcated pale area
Choroidal vessels sometimes white

29. OCT IN DRY ARMD

30. • Atrophic form or “Dry AMD” is defined by areas of RPE atrophy, often resulting
from regression of confluent soft drusen.
• areas of atrophy, usually perifoveal, gradually spread to become confluent,
forming a partial, then complete ring, and finally involving the center of the
macula.
• Histologically, RPE atrophy is accompanied by a loss of the outer nuclear layer,
and the outer plexiform layer becomes in direct contact with basal laminar
deposits.

31. • Dry AMD is characterized by the absence of an exudative reaction.
• Thinning and loss of the RPE are clearly visualized, but maintenance of the
straight line representing Bruch’s membrane is an important sign.
• The external limiting membrane and IS/OS interface are severely altered
and/or no longer visible and become disrupted early.
• In the most severe forms, the outer nuclear layer is no longer visible in the
zones of atrophy.
• The outer plexiform layer comes directly in contact with Bruch’s membrane.

32. DRY AMD –INITIAL STAGE
The external limiting membrane was readily visible almost everywhere and was
raised by numerous drusen. In area of atrophy , the IS/OS interface and external
limiting membrane were no longer visible and were replaced by a moderately
dense zone masking the outer nuclear layer

33. SAME PATIENT AFTER 6 MONTHS
localized juxtafoveal atrophy in the de-pigmented area of the RPE, which was now
clearly visible.
In this zone, the outer retinal layers were no longer visible, apart from the outer
nuclear layer.
There is RPE at the edges of the atrophy and the alterations of the outer retinal
layers over each large drusen.

34. SAME PATIENT AFTER 1 YEAR
the area of atrophy was slightly larger and the outer nuclear layer had completely
disappeared in this zone, which induced a juxtafoveal scotoma that interfered with
reading

35. EXTRAFOVEAL DRY AMD
RPE was clearly visible with numerous drusen. Atrophy of the RPE over the hyper-fluorescent spots
and visibility
of the straight line of Bruch’s membrane with marked back-shadowing.
Anterior to the RPE, the ELM and IS/OS interface were clearly visible and were disrupted over the
area of atrophy.
Disruption of the ELM and IS/OS interface and especially loss of the outer nuclear layer.
The outer plexiform layer was in contact with Bruch’s membrane.

36. Dry AMD: Advanced Perifoveal and Subfoveal
Form
anterior to the RPE, the IS/OS interface and external limiting membrane were no longer visible over
the zone of atrophy.
The outer nuclear layer was also lost, bringing the outer plexiform layer in contact with Bruch’s
membrane, which confirmed the localized atrophy of the RPE and photoreceptors in this zone.

37. Macular Atrophy Following RPE Tear
In the elevated zone, the RPE was irregular, rolled up, and hyper-reflective (reactive proliferation of
the RPE that invaded all of the outer retinal layers). The IS/OS interface and external limiting
membrane were occasionally visible
but not clearly identified.
In the atrophic zone, the outer retinal layers were absent, bringing the outer plexiform layer in contact
with Bruch’s membrane and confirming photoreceptor atrophy.

38. Macular Atrophy due to Vitelliform Macular Dystrophy
Spectralis* horizontal section: almost complete
disappearance of the RPE in the central subfoveal zone.
Persistence of several scattered hyper-reflective islands
anterior to Bruch’s membrane. Loss of the IS/OS
interface. The ELM and outer nuclear layer were normal
Spectralis* vertical section: the RPE was preserved but
with accumulation of fairly dense hyper-reflective
material that appeared to proliferate anteriorly in the
outer nuclear layer.

39. The typical SD-OCT characteristics of geographic atrophy include
• Loss of the outernuclear layer (ONL)
• Loss of the outer hyperreflective bands (external limiting membrane
[ELM], ellipsoid zone, interdigitation zone, inner part of the RPE-
Bruch’s membrane [BM] complex resulting in direct apposition of the
outer plexiform layer (OPL) and BM
• A choroidal signal enhancement that is explained by increased
penetration of the light through the area of RPE atrophy

40. Baseline visit shows a large drusenoid retinal pigment
epithelial detachment (PED) with signs predictive for
pending atrophy such as hyper-reflective foci ( arrow
) and hyper-transmissions within the PED (
arrowhead ), presumably due to RPE breakdown.
After 1 year the large drusenoid PED has partially
collapsed with an adjacent area of outer retinal
subsidence ( arrow ), a sign for nascent geographic
atrophy (nGA).
Two years after baseline the PED has completely
collapsed, leaving drusen-associated atrophy with the
characteristic hyper-transmission into the choroid (
area between arrows ) resulting from loss of the
RPE,photoreceptor, and choriocapillaris

41. The typical SD-OCT characteristics of geographic atrophy include
• Loss of the outernuclear layer (ONL)
• Loss of the outer hyperreflective bands (external limiting membrane
[ELM], ellipsoid zone, interdigitation zone, inner part of the RPE-
Bruch’s membrane [BM] complex resulting in direct apposition of the
outer plexiform layer (OPL) and BM
• A choroidal signal enhancement that is explained by increased
penetration of the light through the area of RPE atrophy

42. Hard Drusen
• Fundus photograph of the
right eye showing multiple
discrete drusen at the fovea
• Arteriovenous phase showing
discrete early
hyperfluorescence
• The hyperfluorescence at the
drusen has increased in the
mid arteriovenous phase
• Fading of the
hyperfluorescence is seen in
the late phase
• The RPE atrophy overlying the
drusen allows the background
choroidal fluorescence to be
seen as transmitted
hyperfluorescence
FFA-DRUSEN

43. Soft Drusen
• Fundus photograph of the RE
showing large soft Drusen
• Faint hyperfluorescence is seen
at the drusen in early AV phase
• Further increase in the
hyperfluorescence is noted
• Maximum hyperfluorescence is
seen in the late phase due to
staining of the soft drusen.
• Due to the hydrophobic nature
of the soft drusen material, the
entry of the dye into the drusen
is delayed. Hence, the soft
drusen do not show
hyperfluorescence until the late
stages.

44. • Fundus photograph showing large
atrophic patches arranged in an
annular fashion around the fovea.
RPE alteration is noted in the foveal
region
• Arteriovenous phase shows relative
hypo-fluorescence in the region of
atrophy. Irregular hyper-fluorescence
is seen at the rest of the macula
• Normal scleral staining is seen
through the atrophic areas making
them appear hyperfluorescent in the
late phase
• Early hypofluorescence within an
atropic lesion indicates non filling of
the underlying atrophic
choriocapillaris along with atrophy of
the RPE
FFA-GEOGRAPHIC ATROPHY

45. DRY AMD: COURSE AND VISUAL
PROGNOSIS
• Patients with only drusen not have much loss of
vision, but require additional magnification of the
text and more intense lighting to read small points.
• Presence of large drusen (>63 microns in diameter)
is associated with a risk of the late form of the
disease like CNV.
• Geographic atrophy- severest form of the dry AMD

46. • AREDS Categories:
– No AMD (AREDS category 1)
• No or a few small (<63 micrometres in diameter) drusen.
– Early AMD (AREDS category 2)
• Many small drusen or a few intermediate-sized (63- 124
micrometres in diameter) drusen, or macular pigmentary
changes.
– Intermediate AMD (AREDS category 3)
• Extensive intermediate drusen or at least one large (≥125
micrometres) drusen, or geographic atrophy not involving the
foveal centre.
– Advanced AMD (AREDS category 4)
• Geographic atrophy involving the foveal centre (atrophic, or
dry, AMD)
• Choroidal neovascularisation (wet AMD)
AMD: STAGING

47. Investigations
• History: Gradual change = non-exudative
Sudden change = exudative
• Visual Symptoms:- VA for Distance and near & improve with PH
Difficulty in reading/recognising faces, driving
Difficulty with changing light / adapting after bright light
Distortion of images mostly with exudative changes
Less common symptoms include night glare, photopsia (flickering
or flashing lights), visual hallucinations (Charles Bonnet syndrome)
& abnormal dark adaptation

48. • Amsler grid test:
Assesses distorted & scotoma , small irregularities in the central field of vision
( 10degree)
• Ophthalmoscopy:
To detect drusen, as well as neovascularization
• Fluorescein and ICG angiography:
Determines the presence and location of wet AMD
• Optical coherence tomography

49. MANAGEMENT
• Antioxidants: AREDS-1 study & follow-up AREDS-2 Study
use of high dose of multivitamins & antioxidants decreases the risk of
progression of ARMD in those with high risk characteristics as age >55 with
one or more of following
Extensive intermediate or
At least one large Drusen
GA in one or both eyes
Late AMD in one eye ( greatest benefit in AREDS1)
AREDS1 Formula AREDS2 Formula
Vitamin E 400IU Vitamin E 400IU
Vitamin C 500mg Vitamin C 500mg
Beta Carotene 15mg ( Vit A 2500IU) Leutin 10mg
Zinc 80mg Zeaxanthin 2mg
Copper (Cupric Oxide) 2mg Zinc 25-80mg
Copper 2mg

50. D iagnosis Recommended
Treatment
Observation with no
medical or
surgical therapies
Antioxidant vitamin and
mineral
supplements as
recommended
in the AREDS reports
No clinical signs ofAMD
(AREDS category 1)
Early AMD
(AREDS category 2)
Advanced AMD with bilateralsubfoveal
geographic atrophy or disciform scars
Intermediate AMD
(AREDS category 3)
Advanced AMD in oneeye
(AREDS category 4)

51. • Dry ARMD:-
1) Antioxidant supplimentation & Risk factors modulation
2)Low Vision Aids
3)Anti-inflammatory drugs-
• Sirolimus (Rapamycin) macrolide,obtained from
fungus, immunosuppressant & used intravitreal
• Intravitreal Steroids as FA implants (sustain release
upto 36 months)

52. 4. Complement Inhibition-
• POT-4 neutralize early AMD inflammatory
component & it is a Intravitreal gel sustain release
system
• ARC1905 a C5 inhibitor Aptamer prevents C5a
production
• Eculizumab a Antibody against C5, currently
approved only for PNH
• Lampalizumab a monoclonal antibody, used as
intravitreal monthly
5. Neurotrophic Factors-
NT501 a genetically modified RPE intravitreal implant,
shown retinal thickness as early as 4 months.
6. AL-8309A-
topical solution, light induced oxidative damage

53. 7) Reduction of Retinal Toxins-
In Dry AMD lipofuscin (a waste products) accumulates at
leading edge of lesion ACU-4429 & Fenretinide (Oral doses)
prevents accumulation of lipofuscin
8)Choroidal Blood Perfusion Enchancers-
MC-1101 as Topical drug, shown to increase mean
choroidal blood flow
9)Other Options
Photocoagulation of Drusen
Saffron (20mg/day) a neuroprotective effect
Intravitreal neuroprotective drug Brimonidine
Surgery like Retinal translocation, Subretinal
Stem cell Transplantation

55. REHABILATATION
• Low vision aids-
– Individual who
experiences
untreatable visual
loss & effects the
daily life.
– Reading lamps &
simple magnifiers
may be beneficial.
– Closed circuit television
& scanning devises are
also available to provide