1

Bird 1995, p367A,B;

NEI 2012, p1A;
de Jong 2006, p1475B
NEI 2012, p1A,5A;
de Jong 2006, p1474A

NEI 2012, p7A

de Jong 2006, p1475B

Key Points
This slide provides a basic definition of AMD
1-3
Bird 1995, p367A,B;AMD is a chronic degenerative condition associated with aging that is characterised by loss of central vision
NEI 2012, p1A,5A; Untreated or suboptimally treated AMD may lead to irreversible vision loss 2,3
de Jong 2006, The international classification of AMD
p1474A,1475B
Early AMD is mainly characterised by soft drusen and retinal pigment epithelium (RPE) pigment changes
NEI 2012, p7A
de Jong 2006, p1475B Late AMD is mainly defined as follows:
Dry AMD or geographic atrophy is characterised by
Any sharply delineated, roughly round or oval area of hypopigmentation or depigmentation or apparent
absence of the RPE in which choroidal vessels are more visible than in surrounding areas that must
be 175 m in diameter
Wet AMD (wAMD), also called neovascular AMD, disciform AMD, or exudative AMD, is characterised by
any of the following:
RPE detachment(s), which may be associated with neurosensory retinal detachment
Subretinal or sub-RPE neovascular membrane(s)
Epiretinal, intraretinal, subretinal, or subpigment epithelial scar/glial tissue or fibrin-like deposits
Subretinal haemorrhages that may be nearly black, bright red, or whitish-yellow and that are not related
to other retinal vascular disease
Hard exudates (lipids) within the macular area related to any of the above and not related to other
retinal vascular disease

References
1. Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related
maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv
Ophthalmol. 1995;39(5):367-374.
2. National Eye Institute. National Institutes of Health. Facts about age-related macular degeneration. 2012.
http://www.nei.nih.gov/health/maculardegen/armd_facts.asp. Accessed March 11, 2012.
3. de Jong PTVM. Age-related macular degeneration. N Engl J Med. 2006;355(14):1474-1485.
4. Fletcher, E. (2008). Retina in P. Iodan-Eva & J. P. Whitcher (Eds.), Vaughan & Asburys General Ophthalmology (17th ed.,
pp. 186211). New York: McGraw Hill.

2
 Fletcher 2008, p188A Fletcher 2008, p188A

Fletcher 2008, p188A,B;

Fletcher 2008, p187A;
AAO R&V 2012, p57A
AAO R&V 2012, p57A

Fletcher 2008, p188B Fletcher 2008, p188B

Key Points

Fletcher 2008, p187A; Drusen are visualised clinically as yellow deposits, situated within Bruch's membrane1
AAO R&V 2012, p57A
They vary in size and shape and may appear as discrete yellowish, waxy-looking spots
Fletcher 2008, p187A;
AAO R&V 2012, p57A or cover a confluent area
1

Drusen accumulation may lead to one of 2 types of age-related macular degeneration:

Fletcher 2008, p187A;
AAO R&V 2012, p57A
dry AMD or wet AMD1
Dry AMD2
Fletcher 2008, p188A
Manifests as well-demarcated areas, larger than 2 disc diameters, of atrophy of the retinal
pigment epithelium and photoreceptor cells, allowing direct visualisation of the underlying
choroidal vessels
Visual loss occurs once the fovea is affected
Wet AMD2
Fletcher 2008, p188B Is characterised by the development of choroidal neovascularisation or serous retinal pigment
epithelial detachment
Choroidal new vessels may grow in a flat cartwheel or sea-fan configuration away from their site
of entry into the subretinal space to form a choroidal neovascular membrane
Haemorrhagic detachment of the retina may undergo fibrous metaplasia, resulting in an elevated
subretinal mass called a disciform scar
Permanent loss of central vision ensues
References
1. Fletcher EC, Chong NHV, Shetlar DJ. Retina. In: Riordan-Eva P, Whitcher JP, eds.
Vaughan & Asburys General Ophthalmology. 17th ed. New York, NY: Lange
Medical Books/McGraw-Hill; 2008:186-211.
2. Retina and Vitreous. In: Basic and Clinical Science Course. 2012-2013 ed. San Francisco, CA: American

3
Academy of Ophthalmology; 2012:55-88.

3
4
Data for geographical atrophy (GA) AMD neovascular AMD show similar increases
(data available from the authors)1
Late AMD is defined either by the international classification or by the Wisconsin
system.2,3
International classification: a degenerative disorder in persons 50 years of age with the following abnormalities
in the macular area on fundoscopy: soft drusen 63 , hyper/hypo- pigmentation of the retinal pigment
epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal haemorrhages, geographic atrophy
of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Late disease
includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE
detachment, haemorrhages, and/or scars as described above)
Wisconsin system: late AMD is defined when there are signs of geographic atrophy or exudative age-related
maculopathy.

References
1. Owen CG et al. Br J Ophthalmol. 2012;96:752756
2. Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related
maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.
Surv Ophthalmol 1995;39:367e74.
3. Klein R, Davis MD, Magli YL, et al. The Wisconsin age-related maculopathy grading system. Ophthalmology
1991;98:1128e34.

5
AAO 2011, p4B

Eong 2007, p57A,B

Eong 2007, p65A

Eong 2007, p63A

Eong 2007, p68A

Eong 2007, p77B

Key Points
Established risk factors for AMD may be characterised as modifiable or non-modifiable
- Non-modifiable risk factors include
AAO 2011, p4B Age: the main risk factor for the development of AMD is increasing age1
Eong 2007, p57A,B Genetic factors: relative risk of developing AMD for first degree relatives of patients varies
between about 2 and 3 2,3
absolute risk estimate is 48% for relatives of AMD patients versus 23% for
relatives of patients without AMD (P=0.001; 90% concordance between
Eong 2007, p65A
monozygotic twin pairs)2
Eong 2007, p63A Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related
Eong 2007, p68A maculopathy.Am J Ophthalmol. 1997;123(2):199-206.3

- Modifiable risk factors include

AAO 2011, p4B,5A Cigarette smoking2
Eong 2007, p77A Body mass index (BMI), waist circumference, and waist-to-hip ratio2
Eong 2007, p77A Low levels of antioxidant enzymes2
Eong 2007, p77C Other putative risk factors that may play a role in AMD and have been cited in prior literature, but have
not been proven or disproven, include
- Cardiovascular disease1
- Light iris colour2
- Sunlight exposure2
- Hyperopia2
References
1. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern Guidelines. Age-
Related Macular Degeneration. San Francisco, CA: American Academy of Ophthalmology; 2011.
http://www.aao.org/ppp. Accessed January 13, 2012.
2. Eong KA, Maheshwar B, Beatty S, Haller JA. Risk factors for age-related macular degeneration and

6
 choroidal neovascularization. In: Lim JI, ed. Age-Related Macular Degeneration. 2nd ed. New York,
NY: Informa Healthcare USA; 2007:47-85.

3. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy.Am J
Ophthalmol. 1997;123(2):199-206.

6
Brown 2005, p1A

Brown 2005, p1A

Key Points1
This table compares the impact of AMD on quality of life (QOL) with other chronic conditions
Mild AMD caused a 17% decrease in the QOL of the average patient, similar to that encountered with moderate
cardiac angina or symptomatic human immunodeficiency virus (HIV) syndrome
Moderate AMD caused a 32% decrease in the average patients QOL, similar to that associated with severe cardiac
angina or a fractured hip
Severe AMD caused a 53% decrease in QOL; more than that of dialysis
Very severe AMD caused a 60% decrease in the average AMD patients QOL, similar to that encountered with end-
stage prostate cancer or a catastrophic stroke that leaves a person bedridden, incontinent, and requiring constant
nursing care
Patients with varying degrees of severity of AMD were found to have QOL impairment ranging from 96% to 750%
greater than that estimated by ophthalmologists who treat AMD
Reference
1. Brown GC, Brown MM, Sharma S, et al. The burden of age-related macular degeneration: a value-based
medicine analysis. Trans Am Ophthalmol Soc. 2005;103:173-184.

7
8
9
10
11
12
13
FAF imaging gives information over and above conventional imaging techniques in
various retinal disorders .
It is not time-consuming,
easy to perform,
noninvasive imaging method.
Particularly in disorders of the outer retina,
the application offers the opportunity to identify disease-related abnormalities and to
determine the integrity of the RPE.

14
n atrophic AMD, atrophy areas appear as sharply demarcated areas with
depigmentation and enhanced visualization of deep choroidal vessels on fundus
photograph (left). At the corresponding fundus autofluorescence image (right),
atrophic patches are clearly delineated by decreased intensity and high-contrast to
non-atrophic retina. Surrounding atrophy, in the junctional zone of atrophy, levels of
marked FAF intensity are observed which are invisible on fundus photography. These
abnormalities tend to precede atrophy over time and may serve as disease markers.

15
. Monitoring of atrophic progression over time with fundus autofluorescence
imaging, showing the natural course of the disease over 5 years. Note, the preserved
foveal island ("foveal sparing") in the center of the central atrophic patch, which
becomes smaller during the review period

16
17
Fletcher 2008, p187B

Fletcher 2008, p187B

Fletcher 2008, p187B

Fletcher 2008, p187B

Fletcher 2008, p187A

Fletcher 2008, p187B

Fletcher 2008, p187B

Fletcher 2008, p187B

Key Points1,2,3
Fletcher 2008, p187B
The pathogenesis of AMD is not completely understoodongoing research may provide
greater insights
Degeneration of the retinal pigment epithelium, linked to oxidative stress, seems to be a
crucial component
Changes in the adjacent extracellular matrix of Bruch's membrane and the formation of
subretinal deposits are central to disease progression
Progressive diffuse thickening of Bruch's membrane reduces the ability of oxygen to
diffuse through to the retinal pigment epithelium and photoreceptors
The resulting hypoxia results in release of growth factors and cytokines, which stimulate
growth of choroidal new vessels
Development of single or multiple areas of weakness in Bruch's membrane allows the
new vessels to grow through into the subretinal space, between the retinal pigment
epithelium and the retina, to form a choroidal neovascular membrane
The new vessels leak serous fluid and/or blood, resulting in distortion and reduction of
clarity of central vision
Alternatively, visual loss results from progression of the degenerative process to cell
death and atrophy of the retinal pigment epithelium
Reference
1. Fletcher EC et al. Retina in: Vaughan & Asburys General Ophthalmology. 2008:186-211.
2. Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy
Pharmacological Reports 2006;58(3):35363.
3. Winkler B set al. Oxidative damage and age-related macular degeneration. Molecular
vision. 1999;5:32.

18
See Notes for annotations

Key Points
Oliver 2007, p161A CNV is the hallmark of wAMD pathophysiology and is defined as the proliferation of the choroidal capillaries through a break in
AAO 2011, the outer aspect of Bruchs membrane under the RPE and/or the neurosensory retina1
p13ABCD, 14AB CNV is determined clinically and by classified slightly differently by different imaging techniques (eg, fluoresceien angiography,
FA , optical coherence tomography, OCT, and indocyanine green angiography, ICG) 2
AAO 2011, p6A; There are 4 main types of CNV, defined as follows:
Freund 2010,
Type 1 (which is similar to the occult type of CNV originally identified on FA) the most common form and characterised by
p1335B
fibrovascular pigment epithelial detachment, an irregular elevation of the RPE with stippled or granular irregular
Freund 2010, fluorescence first seen early in the angiogram, and progressive leakage in the later phase of the angiogram2,3
p1335B Patients lesions are not well defined, and they have less leakage than the classic subtypes 3
AAO 2011, p6A; Type 2 (most similar to the original classic type on FA) an area of bright, fairly uniform hyperfluorescence identified in the
Freund 2010, early phase of the angiogram, with progressive pooling of dye in the overlying sensory retinal space during the late phase
p1335A of the angiogram2,3
Predominantly ClassicThis subtype has the most aggressive disease pathology and accounts for approximately
AAO 2012, p2A 25% of wAMD cases. Studies suggest that this subtype leads to more rapid vision loss than the other subtypes.
Lesions in the classic forms are well defined4
Minimally ClassicThis subtype has a less rapid rate of vision loss than the predominantly classic subtype, and
AAO 2012, p2B together with the occult subtype, accounts for the remaining 75% of wAMD cases 4
Type 3/RAPproliferation of the retinal capillaries in the paramacular area2,3
AAO 2012, p28A; PCVcharacterised by peripapillary location, absence of drusen, and is the principal vascular composition of patients of
Freund 2010, 1335A pigmented races experiencing neovascular maculopathies, particularly African Americans and Asians1,5
Oliver 2007, References
p163A; 1. Oliver SCN, Ciardella AP, Ferrara DCAC, et al. Indocyanine green angiography in age-related macular
Imamura 2010, degeneration. In: Lim JI, ed. Age-Related Macular Degeneration. 2nd ed. New York, NY: Informa Healthcare
p503A, 505A USA; 2007:159-175.
2. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern Guidelines. Age-Related Macular
Degeneration. San Francisco, CA: American Academy of Ophthalmology; 2011. http://www.aao.org/ppp. Accessed January
13, 2012.
3. Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular
degeneration? Retina. 2010;30(9):1333-1349.
4. American Academy of Ophthalmology. Dry and wet AMD. http://www.aaofoundation.org/what/AMD/DryWetAMD.cfm.
Accessed June 8, 2012.
5. Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol.
2010;55(6):501-515.

19
See Notes for annotations

Key Points
Oliver 2007, p161A CNV is the hallmark of wAMD pathophysiology and is defined as the proliferation of the choroidal capillaries through a break in
AAO 2011, the outer aspect of Bruchs membrane under the RPE and/or the neurosensory retina1
p13ABCD, 14AB CNV is determined clinically and by imaging techniques (eg, FA, OCT, ICG)2
There are 4 main types of CNV, defined as follows:
AAO 2011, p6A; Occult (Type 1)the most common form and characterised by fibrovascular pigment epithelial detachment, an irregular
Freund 2010,
elevation of the RPE with stippled or granular irregular fluorescence first seen early in the angiogram, and progressive
p1335B
leakage in the later phase of the angiogram2,3
Freund 2010, Patients lesions are not well defined, and they have less leakage than the classic subtypes 3
p1335B Classic (Type 2)an area of bright, fairly uniform hyperfluorescence identified in the early phase of FA, with progressive
AAO 2011, p6A; pooling of dye in the overlying sensory retinal space during the late phase of the angiogram2,3
Freund 2010, Predominantly ClassicThis subtype has the most aggressive disease pathology and accounts for approximately
p1335A 25% of wAMD cases. Studies suggest that this subtype leads to more rapid vision loss than the other subtypes.
Lesions in the classic forms are well defined4
AAO 2012, p2A Minimally ClassicThis subtype has a less rapid rate of vision loss than the predominantly classic subtype, and
together with the occult subtype, accounts for the remaining 75% of wAMD cases 4
RAP (Type 3)proliferation of the retinal capillaries in the paramacular area2,3
AAO 2012, p2B PCVcharacterised by peripapillary location, absence of drusen, and is the principal vascular composition of patients of
pigmented races experiencing neovascular maculopathies, particularly African Americans and Asians1,5
AAO 2012, p28A; References
Freund 2010, 1335A1. Oliver SCN, Ciardella AP, Ferrara DCAC, et al. Indocyanine green angiography in age-related macular
Oliver 2007, degeneration. In: Lim JI, ed. Age-Related Macular Degeneration. 2nd ed. New York, NY: Informa Healthcare
p163A; USA; 2007:159-175.
Imamura 2010, 2. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern Guidelines. Age-Related Macular
p503A, 505A Degeneration. San Francisco, CA: American Academy of Ophthalmology; 2011. http://www.aao.org/ppp. Accessed January
13, 2012.
3. Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular
degeneration? Retina. 2010;30(9):1333-1349.
4. American Academy of Ophthalmology. Dry and wet AMD. http://www.aaofoundation.org/what/AMD/DryWetAMD.cfm.
Accessed June 8, 2012.
5. Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol.
2010;55(6):501-515.

20
NEI 2012, p5A

NEI 2012, p5A

NEI 2012, p2A,5A

NEI 2012, p5A

NEI 2012, p5A

Morgan 1995, p526A

Morgan 1995, p526A

Key Points
This slide presents common AMD symptoms
NEI 2012, p5A Well-defined blurry spot or blind spot1
NEI 2012, p5A Decreased central vision1
NEI 2012, p2A, 5A Decreased intensity or brightness of colours1
NEI 2012, p5A
Distorted images and lines1
Morgan 1995, p526A Glare and reduced night vision2,3
References
1. National Eye Institute. National Institutes of Health. Facts about age-related macular
degeneration. 2012. http://www.nei.nih.gov/health/maculardegen/armd_facts.asp.
Accessed March 11, 2012.
2. Morgan R, King D. The older drivera review. Postgrad Med J. 1995;71(839):525-528.
3. Ying, Gui-Shuang; Maguire, Maureen G; Liu, Chengcheng; Antoszyk, Andrew N. Night
vision symptoms and progression of age-related macular degeneration in the
Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology
2008;115(11): 1876-82.

21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
In Stargardt macular dystrophy, fundus pathology is better detected with fundus
autofluorescence imaging than fundus photography. Typically, autofluorescence
imaging shows a central oval area of reduced signal surrounded by small
disseminated spots of reduced and increased intensity. There is also central
multifocal RPE atrophy present showing very decreased FAF intensity. Yellowish-
appearing flecks on fundus photography correspond to punctate spots with bright
autofluorescence signal.

87
88
. Idiopathic juxtafoveal telangiectasia Type 2a shown by fundus photography (A),
fundus autofluorescence (B) and early- (C) and late-phase (D) fluorescein
angiography. No obvious alterations are visible by fundus photography. Fluorescein
angiography shows telangiectatic vessels in the parafovea and late-phase
hyperfluorescence. Fundus autofluorescence imaging reveals markedly increased
levels of the central fovea as opposed to the typical decreased signal in normal
subjects.

89
90
 early hydroxychloroquine toxicity can demonstrate mottled areas of increased AF,
which without intervention can progress to areas of decreased AF and atrophy, with a
typical bull's-eye configuration.

91
92