Age Related Macular Degeneration (AMD) is a degenerative disorder affecting the macula characterized by drusen and RPE changes in the absence of other disorders. It is classified as dry or wet. Dry AMD includes early, intermediate, and dry advanced AMD. Wet AMD is neovascular and can be classic or occult. The risk increases with age, especially after age 50. Treatment includes antioxidants, lifestyle changes, and for wet AMD, anti-VEGF agents are the first line treatment administered every 4-8 weeks.

1. Age Related Macular
Degeneration

2. INTRODUCTION
• Degenerative disorder affecting the macula
• Characterized by the presence of specific
clinical findings like drusen and RPE changes in
the absence of another disorder

3. TYPES
• DRY – non neovascular: includes
- Early
- Intermediate
- Dry type of advanced AMD
• WET – neovascular

7. Epidemiology
• The WHO estimated in 2002 that 8.7/ of world
blindness was due to AMD.
• AMD rare before the age of 55 and more
common in person 75 years of age and older.
• The prevalence of advanced AMD increases
with each decade after the age 50.
• Highest prevalence occurring after the age of
80.

8. RISK FACTORS
• Age-major risk factor
• Gender -Female>Male
• Race -White>Blacks
• Family history
• Light exposure
• Hypertension

9. • Smoking
• Drugs – Aspirin ,chloroquine and phenothiazine
• Ocular factors - blue coloured iris, hyperopia,
cataract sx.
• Dietary factors -high fat intake and obesity increases
risk .

10. PATHOPHYSIOLOGY OF ARMD
ARMD is characterized by -
• Drusen formation.
• RPE abnormalities -hyper and hypopigmentation.
• Geographical atrophy of RPE and choriocapillaries.
• Neovascular maculopathy.

11. Drusen
• The earliest clinically detectable sign
• Drusen are tiny pin point,yellow deposits of
abnormal hyaline material located at interface of
Bruch’s membrane and the RPE.
• Rarely present <45yrs
• On H/P - Drusen are focal areas of the
eosinophilic material between the basement
membrane of RPE & BM.

12. HISTOLOGICAL LOCATION OF DRUSEN
INL 
ONL
IS
OS
RPE
CC

13. DRUSEN SIZE
• Small < 63 microns – not a sign of AMD
• Intermediate 63-124 microns
• Large >/=125 micron
• Very large >250 microns
HOW TO MEASURE DRUSEN?????

14. SMALL OR HARD DRUSEN
• Discrete , well demarcated, yellowish white
• Occur with ageing – alone not enough to
classify as AMD
• FFA- pin point window defect
• Risk of progression to advanced AMD – 1.3%
after 5 years

15. SOFT DRUSEN
• > 63 microns
• Located b/w RPE basement membrane & inner
collagenous layer of bruchs membrane
• Intermediate 64- 124 microns
• Large drusen > 124 micron
• Very large drusen > 250 micron
• Decreasing density of the drusen from centre to
the margin
• Tendency to cluster and merge with one another
- coalascence

17. • There is no increases with age
• May spontaneously regress or disappear over
period of time- leaving RPE atrophy
• Eyes with soft drusen are at an increased risk
of developing RPE abnormality, geographic
atrophy and CNV

18. SOFT DRUSENS FFA
• FFA- hyperfluorescence early and fade or stain
in late phase
• Persistent staining is due to pooling of dye in
focal detachment of RPE membrane or
staining of diffuse drusen material
• RPE cells over the soft drusen are hypo
pigmented or atrophic

21. RISKS OF ADVANCED AMD IN LARGE
DRUSEN
Eyes with B/L large drusen
• Risk of CNV is 18% in atleast 1 eye in 3 years
• Risk of geographic atrophy – 8%
Eyes with large drusen with CNV in one eye
• Large drusen present – 46% risk of CNV in
good eye in 5 yrs
• If no large drusen 10% risk only

22. SPECIAL TYPES OF DRUSEN
• Cuticular drusen
• Pseudodrusen or subretinal drusen or
subretinal drusenoid deposit

23. CUTICULAR DRUSEN
• Small( like hard drusen) but are more numerous
than hard drusens and extend beyond arcades
upto mid periphery
• Located betweeen RPE basement membrane and
inner collagenous layer of bruchs membrane
• FFA- starry night appearance due to RPE atrophy
over the drusen
• FAF- Mild decrease in FAF over the drusen
• OCT- triangular or saw tooth appearance

25. SUBRETINAL DRUSENOID DEPOSITS
• Pseudo drusens or reticular drusens
• Located internal to the RPE between RPE and
sensory retina
• Composition is like soft drusen
• Appear as white or blue and are better seen with
blue light
(blue light not filtered as they are above the RPE)
• Network like appearance seen- reticular
• More in perifoveal region

26. Dry AMD
(1)SYMPTOMS:
• Initially none
• Difficulty in dark adaptation
• Decreased vision
(2) SIGNS:
• Intermediate- large soft drusen
• RPE hypo/hyperpigmentation
• Geographic atrophy
• Drusenoid RPE detachment

28. (3)OCT FINDINGS:
• Drusens
• Outer retinal tubulations
• Outer retinal corrugations
(4) FA – window defect due to unmasking of
background choroidal fluorescence

29. CHANGES IN RPE IN NON
NEOVASCULAR AMD
• Pigment mottling
• Stippled hypopigmentation
• Focal hyperpigmentation
• Geographic atrophy

30. • PIGMENT MOTTLING AND STIPPLED
HYPOPIGMENTATION
- These occur when the neurosensory retina
thins over the abnormal RPE area
- May precede the GA
- RPE overlying the drusens shows
hypopigmentation

31. • FOCAL HYPERPIGMENTATION
- clinically evident pigment clumping at the
level of outer retina or subretinal space
- Maybe punctate, linear or reticular in shape
- Present in 3-12 % of adults >50 yrs
- Higher risk of CNV if focal hyperpigmentation
and soft drusens are present and if the other
eye has CNV 58-73% within 5 years

33. GEOGRAPHIC ATROPHY
• Advanced form of dry AMD when it involves the
fovea
• RPE atrophies in well defined round area with
atrophy of underlying choriocapillaries- so large
choroidal vessels seen easily
• These start as round areas often ringing the fovea
and then coalesce and enlarge and ultimately
involve the fovea
• Upto 20% of cases of legal blindness due to AMD
are caused by geographic atrophy

34. Contd…
• The area of geographic atrophy has atrophic
RPE and choriocapillaries  atrophy of
photoreceptor layer  scotoma
• If it involves the fovea then V/A can drastically
decrease
• GA then becomes advanced form of AMD
**Risk of developing CNV at the edge of GA**
• FFA – RPE window defect

37. HOW DOES GA ARISE?
1. Areas of confluent large drusens may regress
and leave irregular shaped areas of GA
2. Small foci of pigmentory mottling areas may
coalesce and progress to a single area of GA
3. Spontaneous flattening of the RPE
detachment may result in GA

38. • Thin fovea no rpe choroid hyperrefl
• oct

39. INVESTIGATIONS
• Amsler grid test:- Assesses distorted &
scotoma , small irregularities in the central
field of vision ( 10degree)
• Ophthalmoscopy:- to detect
drusen,neovascularization

40. • Fluorescein and ICG angiography:-
Hyperfluorescent lesions:
• Hard and soft drusen
• RPE atrophy
• RPE tear
• CNV
• Serous PED
• Subretinal fibrosis
Hypofluorescent lesion
• Haemorrhage, lipid

41. MANAGEMENT OF DRY ARMD
• Education and follow up:- Periodic
examinations are advised
• Amsler grid test:- Check for visual changes
regularly

42. Antioxidants:- use of high dose of multivitamins &
antioxidants decreases the risk of progression of
ARMD in high risk pt.
– Extensive intermediate Drusen
– At least one large Drusen
– non central GA in one or both eyes
– Late AMD in one eye
REDUCES RISK OF PROGRESSION TO ADVANCED AMD BY
25%

43. Combination of antioxidants vitamins
and minerals-
AREDS1 Formula
• Vitamin E 400IU
• Vitamin C 500mg
• Beta Carotene 15mg ( Vit A 2500IU)
• Zinc 80mg
• Copper (Cupric Oxide) 2mg

44. AREDS2 Formula
• Vitamin E 400IU
• Vitamin C 500mg
• Leutin 10mg
• Zeaxanthin 2mg
• Zinc 25-80mg
• Copper 2mg

45. • Lifestyle changes-obesity reduction and
smoking cessation.
• Avoiding UV light
• Low vision aids - E readers,smart phone,tablets
• Piggy back IOL for near vision (Sharioth IOL)
• Laser photocoagulation- for drusen reduction
EXPERIMENTAL SX-
(1) Miniature intraocular telescope implantation
(2) Retinal translocation surgery

46. • Intravitreal injection of LAMPALIZUMAB(
complement factor d antibody)- FAILED TRIAL
• Intravitreal brimonidine( neuroprotective) and
zimura( inhibits splitting of c5- membrane attacking
complex) under trial
• Visual cycle modulation: ameliorating the formation
of cytotoxic products by reducing the rate of vitamin
A processing. Clinical trials( eg feretinide, emixustat)
underway
• Photocoagulation of drusen leads to a substantial
reduction in their extent, does not reduce the risk of
progression to AMD.
• Saffron(20 md/day)- short term improvement
• Other therapeutic options – subretinal stem cell
transplantation, intravitreal injection of a range of
drugs including ciliary neurotrophic factor

47. RETINAL PIGMENT EPITHELIUM
DETACHMENT
• Due to disruption of physiological
forces which maintaining adhesion.
• Reduction of hydraulic conductivity of
thickened Bruchs Membrane
• Appear as sharply demarcated, dome
shaped elevations of RPE

48. Four types of PED
• Serous PED - may or may not overlie CNV
• Fibrovascular PED - is a form of occult CNV
• Drusenoid PED - does not have CNV,large soft
drusen,often bilateral
• Haemorrhagic PED - always have underlying
CNV or PCV

51. RPE tear
• Tear occur at junction of attached and
detached RPE
• Crescent shaped pale area of RPE dehiscence
next to darker area due to retracted & folded
flap
• It can occur spontaneously, following laser or
after intravitreal

53. Wet AMD
• Break in bruchs membrane is a trigger for
CNV
• Buds of neovascular tissue from
choriocapillaries perforate the outer aspect
of bruchs membrane

55. TYPES OF WET AMD(MACULAR
PHOTOCOAGULATION STUDY)
(1) Type I: - occult CNV (80%)
• The fibrovascular complex proliferates betweeen
the bruchs membrane of RPE and inner collagen
layer of Bruch’s membrane
• This FV complex destroys the normal
architecture of choriocapillaries, Bruch’s and
RPE.
• Seen in 2 forms
– PED- fibrovascular pigment epithelium detachment
– Late leakage of an undetermined origin

56. TYPE 1 CNV IN SUB RPE SPACE
• May leak fluid under the RPE causing its detachment
• Fluid may accumulate below the RPE lifting it up from
Bruch’s membrane
• CNV can bleed causing haemorrhagic RPE detachment
• Fluid may appear in sub retinal space – serous RD
clinical or OCT
• Sub RPE blood may break into subretinal space and
rarely break into vitreous- subhyaloid haemorrhage
and vitreous haemorrhage
• The fibrovascular complex may scar and form disciform
scar

58. (2) Type II: Classic CNV (20%)
• It can grow through RPE and reach subretinal space- type II
CNV
• Types
– Subfoveal
– Juxtafoveal
– extrafoveal
• F.A.- Dye fills in a well defined “lacy pattern”
• Subsequent leakage into subretinal space pver 1-2 minutes
• Most CNV – subfoveal
• OCT- Subretinal hyperreflective material
• Present above RPE

60. Clinical features
History:-
• Gradual change in non-exudative ARMD
• Sudden change in exudative ARMD
Symptoms:-
• VA reduced for both distance and near; no
improvement with PH
• Metamorphopsia
• Photopsia
• Abnormal dark adaption

61. SIGNS OF WET AMD
• Presence of SRF- serous retinal detachment in the macula
• Subretinal blood( bright red)
• RPE detachment- hemorrhagic RPE detachment appears
darker
• Subretinal / intraretinal lipids
• Subretinal pigment ring
• Cystoid macular edema
• Subretinal grey white lesion- type 1
• Sea fan pattern of subreinal small vessels- type 2
• RPE rip
• Disciform scar

62. FFA IN WET AMD
• Earliest frame where leakage starts defines
the CNV lesion
• Classic CNV
–well demarcated area of intense
hypofluorescence
-leakage progresses into late phase and usually
obscures the boundary

63. CLASSIC CNV - II
• Well demarcated area of intense hyperfluorescence
appearing early and showing progressive leakage
• Fluorescence most intense at the perimeter of the CNV
• Centre may show hypofluorescence
• Leakage progresses into the late phase of the
angiogram and usually obscures the boundary of the
CNV
• Classsic description of visible subretinal vascular
network (lacy) is seen in minority of eyes with AMD
• Many times occult component will also be seen

65. CLASSIC CNV (according to location)
• Subfoveal :any part of the lesion is located
below the centre of the fovea
• Juxtafoveal : the edge of the CNV is more than
1 micron from the centre of the FAZ and
within 200 microns
• Extrafoveal : the central border of the CNV is
beyond 200 micron from the centre of FAZ

66. PED
• Fibrovascular PED
• Irregular elevation of RPE with stippled or
granular irregular fluorescein is seen usually
about 1-2 minutes after dye injection
• Best seen with - stereo angiogram
• Progressive leakage occurs and causes a
stippled hyperfluorescence that is not intense
as cassic

67. ANGIOGRAPHIC SUBTYPE OF CNV
• In eyes with combination of CNV :
(1) Classic :classic components >50% of total
lesion area
(2) Minimally classic: 1-50% rest occult part
(3) Occult : no classic component

69. FACTS ABOUT CNV
• Most lesions are subfoveal and occult
• 20% subfoveal lesions are predominantly
classic
• Approximately half of juxtafoveal and
extrafoveal lesions are predominantly classic

70. OCT signs of CNV activity
• Intraretinal cyst
• Subretinal cyst
• RPE detachment
• Subretinal blood
• Subretinal tissue

72. ICG
• Longer infra red wavelength can penetrate
RPE and choroid
So it is useful in cases of :
• Occult CNV or poorly defined CNV
• CNV with overlying hge or fluid or exudate
• Distinguish serous from vascularized portions
of fibrovascular PED

74. Variants of neovascular AMD
Retinal angiomatosis proliferans
• Predominantly intraretinal neovascularization
• Frequently Bilateral & Symmetrical
• K/A Type-III neovascular AMD

76. MANAGEMENT OF WET ARMD
A) Anti-VEGF Agents -first line treatment
• Bevacizumab - 1-1.25 mg in0.05ml, repeated 6-8 weekly
• Ranibizumab - First 3 injections of 0.5 mg in 0.05 ml four
weekly and later on physician's assessment
• Aflibercept -2mg in 0.05ml First 3 injections monthly then
every 2 months as maintenance regimen
• Pegatanib - Given 0.3 mg dose six weekly minimum for two
years

77. • Photodynamic therapy-
• I.v. infusion of photosensitizer drug and
application of continuous nonthermal laser light
directed at CNVM
• Wavelength of light used corresponds to
absorption peak of drug
• Application of verteporfin involves 2 steps:
• a) I.V infusion of drug -6mg/m2 over 10mins.
• b) Activation of drug by 689nm light
• MOA- Endothelium damage of new vessels
,Platelet adhesion and thrombosis

78. • Main Indication- Subfoveal predominantly Classic
CNV with visual acuity of 6/60 or better
• Contraindication- Porphyria
• Advantages -
– Highly selective tissue necrosis.
– Scarring is unlikely, as collagen & elastin are
unaffected
– Resistance to treatment does not develop with
repeated treatment
Complications-
– photosensitivity
– acute severe vision decrease (loss of 4 lines within a
week)

79. • Laser Photocoagulation-
• Thermal blue-green Argon laser or diode laser
ablation of CNV
• Modality for juxtafoveal and extrafoveal lesion
• FA should be performed before laser
photocoagulation
Complications are
– Rupture of the pigment epithelium
– Choroidal haemorrhage
– Atrophy of the RPE in the area adjoining
– Accidental treatment of the fovea

80. SURGICAL OPTIONS
• Submacular excision of CNV-
• Useful in management of large subfoveal
haemorrhage where prompt evacuation of blood
limits toxicity to photoreceptor
Technique –
– after pars plana vitrectomy CNVM is removed from
subretinal space by making retinotomy temporal to
fovea and inducing localized retinal detachment
– Lastly fluid-air exchange is performed at end of
surgery and gas tamponade given

81. RPE transplantation-
• CNV excision creates localized RPE defects
with BM abnormalties.
• Lack of RPE ingrowth into dissection bed
results in choriocapillaries and photoreceptor
atrophy
• RPE transplantation improve vision by
reestablishing function of photoreceptors
• RPE cells from donor eyes, stem cells or iris
pigment epithelium

82. Macular translocation-
• Aim -Relocate central neurosensory
retina away from CNV to area of healthier
RPE, bruch membrane and choroid

83. EMERGING TREATMENTS FOR AMD
• Anecortave acetate
– angiostatic steroid that does not exhibit
glucocorticoid receptor-mediated activity 15 mg
delivered as a posterior juxtascleral depot every 6
months.
• Fluocinolone acetonide
– Synthetic hydrocortisone derivative
– Intra-vitreal implant inside the eye
– Sustained release for up to 36 months

84. • Squalamine lactate
– MOA -Blocks the action of VEGF and integrin
expression, thereby inhibiting angiogenesis.
– It is Ineffective intravitreally so given I.V.
• VolociximabIt
– inhibits activity of 5ß1 integrin protein found on
endothelial cells so preventing angiogenesis.
• SphingomabIt
– targeted against sphingosine-1-phosphate which is
implicated in angiogenesis, scar formation, and
inflammation

85. • Sirolimus ( Rapamycin)-
– It Inhibits response of immune system to IL-2 and
blocks T and B-cells activation
– Subconjunctival injection every 2 months for dry
AMD with GA
• Vatalanib
– is a potent inhibitor of all known VEGF receptor
tyrosine kinases, VEGFR1 , VEGFR2 & VEGFR3 .
• Bevasiranib
– silences the genes that lead to the growth of
blood vessels under the retina

86. • Methotrexate –
– It inhibits dihydrofolate reductase, inhibiting
lymphocyte proliferation.
– It is used for wet AMD
• POT-4-
– It inhibit the complement activation system
– Intravitreal gel sustained release system
– Neutralize early AMD inflammatory component

87. • Lampalizumab
– Complement inhibiting monoclonal antibiotic injected
intravitreal on monthly basis, reduced progression of
GA by 44%
• Brimonidine
– Highly selective α2 agonist
– It protects retinal ganglion cells, bipolar cells, and
photoreceptors from degeneration after retinal
ischemia and retinal phototoxicity by upregulating
trophic factors.
– Intravitreal implant, which delivers the drug over a 3-
month period.

88. • Alprostadil –
– Reduction in choroidal blood flow is more
pronounced in patients with AMD These drugs
increase mean choroidal blood flow

89. Gene therapy
• Insertion of functioning gene into human cells
to correct genetic error or to introduce new
function to already existing cells
Molecules for gene therapy include
• VEGF
• Pigment epithelium derived factor (PEDF)
• matrix metalloproteinase (MMP),
• Tissue inhibitor of metalloproteinase (TIMP)

90. THANK
YOU