2. Introduction
• Choroidal neovascularization (CNV) denotes the pathologic growth of new blood
vessels from pre-existing choroidal vessels into the subretinal space
• The newly formed vessels lie between the choroid and the retinal pigment
epithelium (RPE) or between the RPE and the neurosensory retina
• The importance of CNV is that it is the determinant of the disciform process; the
disc-shaped, subretinal, fibrovascular membrane ultimately progresses to
cicatrization, and loss of macular function
6. RISK FACTORS
• Modifiable
• Smoking : 2 fold increase in risk, effect lasts even
after stopping
• Obesity : higher BMI increases the chances
• Anti-oxidants : carotenoids & lutein decreases AMD
• Dietary fat intake
• Hypertension : esp high diastolic BP
• Cardiovascular risk factors
• Cataract surgery
• Sunlight exposure Controversial
7. • Non-Modifiable
• Age : increases with each decade
• Gender : females >> males, esp after 75 yr
• Ethnicity : white >> black
• Genetic factors : familial cases seen in 10-20% cases
• Iris colour : dark colour is protective
8. NORMAL RPE FUNCTIONING
• Most important function of RPE is to engulf parts of the photoreceptors
• Material from the photoreceptors is engulfed and digested by lysosomal
enzymes in the RPE cells and undigested material gets accumulated as
lipofuscin
• Excess lipofuscin decreases the functional capacity of RPE cells and thus
adversely affects the photoreceptor renewal- Basis for onset of macular
degeneration
9. PATHOLOGY AND PATHOPHYSIOLOGY
• Degenerative changes involving the outer portion of the retina, retinal
pigment epithelium, Bruchs membrane and choriocapillaris
10.
11. Photoreceptors & RPE release
VEGF
New vessels grow behind the
macula
Breakdown in the Bruch’s
membrane
Blood vessels are fragile & Leak
blood and fluid
Scarring of macula : Potential
for rapid severe damage
14. Wet AMD
• Painless progressive blurring of vision
Sudden: Subretinal hemorrhage from CNVM
Insidious: Shallow subretinal fluid or PED
15. DRUSENS
• Extracellular hyaline excrescences located between the basement of
RPE and inner collagenous layer of Bruchs membrane
Classified based on the following
• Appearance : Hard, Soft, Calcified
• Size: Small, Large
16. Appearance- Hard, Soft, Calcified
• Hard : small, discrete, well defined , less than 63 microns in diameter
• Soft: Large ill defined, greater than 125 microns, usually raised
• Calcified : Refractile appearance due to deposition of cholesterol and
calcium salts
27. Disciform scar
• End result of CNVM
• Continued exudation, bleeding, proliferation of
vessels, hyperplasia of RPE cells leads to invasion of
fibroblasts and inflammatory cells causing scar
formation
• White and fibrous appearance
30. FFA IN AMD
• Differentiate between Wet and Dry AMD
• Location of CNV in respect to the FAZ
• Determination of the pattern and boundaries
• Determination of treatment and monitoring of response
31. Drusen
Hard: Area of hyperfluorescence which does not increase in space with
time
Soft: Slow filling and not as brightly fluorescent as hard druscen
32. FFA in wet AMD
• Patterns seen are
1)Classic CNVM 2) Occult CNM
Fibrovascular PED
Late leakage from an
undetermined source
33. Classic CNVM
Lacy pattern hyperflourescence in early phase
which increases in intensity and extends
beyond the boundaries of the hyperflourescent
area in mid and late phases
37. • Depending on the amount of hyperfluorescence
Predominantly classic: > 50% of the lesion is classic
Minimally classic: < 50% of lesion is classic
38. • Depending on the location
• Subfoveal: Lesion under centre of fovea
• Juxtafoveal: Lesion between 1-199 microns from the foveal centre
• Extrafoveal: More than 200 microns from the centre
39. ICG IN AMD
• Can pickup choroidal circulation even in the presence of retinal
lesions which would prevent visualisation of FFA
• ICG is useful in
Diagnosing Occult CNVM
Differentiating from IPCV
40. Focal hot spot
Hyperfluorescence
less than 1 DD size
Plaque
Hyperfluorescence
more than 1 DD size
Mixed
Both focal hot spot and plaque
Overlying: Hot spot overlying plaque
Marginal: Hot spot at the margin
Remote: Hot spot away from plaque
41. OCT IN AMD
Drusen
• Appears as local elevation of RPE
• Seen as hypereflectivity
• No optical shadowing
47. Dietary supplementation
• AREDS: High doses of antioxidants reduce risk of progression from
intermediate to advanced AMD by 25%
Formulation of antioxidants
• Zincoxide: 80 mg
• Cupric oxide: 2 mg
• Vitamin C: 500 mg
• Vitamin E: 400 IU
48. ANTIVEGF drugs
• Currently aailable antiVEGFs are
• Pegaptanib sodium ( Macugen)
• Ranibizumab (Lucentis)
• Beacizumab ( Avastin)
49. BEVACIZUMAB (AVASTIN)
-Full-length recombinant, humanized monoclonal antibody
-Binds to all iso--forms of VEGF
-Avastin -1.25mg per 0.05ml
-Rupees 37,000 per vial
-Endophthalmitis, RD, increased IOP Hypertensive crisis,
cardiac failure (these effects are seen with the doses used for
systemic anticancer therapy the ocular dose is far less)
50. Ranibizumab (Lucentis)
-RhuFab (fragment of recombinant, humanized mouse monoclonal
VEGF antibody)
-Binds to all isoforms of VEGF
-Selective destruction of CNV
-Lucentis 0.5 mg (0.05 mL) monthly injections
-Rupees 58,000 per vial (0.23ml)
-Endophthalmitis, RD, increased IOP,Thromboembolic and
cardiovascular events
51. Pegaptanib Sodium
-Aptamer (oligonucleotide composed of single stranded
nucleic acid)
-High affinity to VEGF-165 iso-form
-Macugen solution available single dose,pre-filled syringe 0.3
mg every 6 weeks
-Rupees 47,000 per syringe
-Endophthalmitis, RD,increased IOP Hypertension
-Systemic side effects are less common
54. Anecortave acetate
• Antiangiogenic and inhibits blood vessel growth by decreasing
extracellular protease expression and inhibiting endothelial cell
migration
• Dose of 15 mg in posterior subtenon space and effect lasts for 6
monhts
• Less incidence of raised IOP and cataract
55. LASER Photocoagulation
• Used in extrafoveal and Juxtafoveal lesions
• Argon blue or krypton red laser
• 200 microns spot size
• Burn placed along the inferior border at the non foveal edge of CNVM
followed by foveal edge and should cover an area extending 100microns
beyond the visible lesion
• Endpoint is whitening of the retina
• Complications: Choroidal hemorrhage, Macular pucker, Foeal burn
56. Photodynamic therapy
INDICATIONS:-
1. Subfoveal lesions that are predominantly classic regardless of size
2. Occult lesions with no classic or minimally classic component that
show progression and have documented loss of vision
57. Photodynamic therapy
• Selective destruction of the target lesion while sparing the
surrounding normal tissue.
• Verteporfin (photosensitizer) is selectively taken up by the LDL
receptors in rapidly proliferating endothelial cells of the CNVM.
58. Photodynamic therapy
• Verteporfin -- 6mg/m2 body surface area as an intravenous infusion
over 10 minutes followed by laser treatment after 5 minutes.
• Low intensity laser light (689 nm, energy set at 600 mW/cm2 for 83
seconds) applied subsequently can activate dye and causes
destruction of these cells through a photochemical reaction.
59. Photodynamic therapy
• Avoid exposure to sunlight
• 3 monthly follow up with FFA and OCT
Complications:-
• Choroidal haemorrhage , RPE tears, photosensitivity, hypertension,
Backache, dyspnea and flushing.
60. Transpupillary thermotherapy
• Infrared light of 810 nm is used to destroy CNVM
• Laser energy is absorbed by melanin rich RPE that cuases rise in
temperature in the tissue which results in apoptosis and vessel
coagulation
• 2mm spot at 300 mW power
61. Surgery
• Patient with low visual acuity and predominantly hemorrhagic lesion
not greater than 16 disc areas
• Subretinal surgery, Macular translocation, Vitrectomy
• Complications: Retinal detachment and cataract
62. CLINICAL TRIALS FOR DRY AMD
Name Aim & Methods Conclusion
AREDS (Age
related Eye disease
study)
Evaluate effect of
high doses of
antioxidants & zinc
on progression
Antioxidants & zinc
Comb reduce risk of
developing AMD by
25%
LAST (Lutein
Antioxidant
Supplement Trial)
To evaluate role of
luetin and
antioxidants in AMD
lutein+antioxidants
showed 50%
increase in avg
macular
Pig. optical density
63. CLINICAL TRIALS FOR WET AMD
Name Aim & Methods Conclusion
MPS (Macular
Photocoagulation
Study)
-Argon blue-green
laser Photo
coagulation in
extrafoveal
-Krypton red laser in
juxtrafoveal
Photocoagulation is
effective in all well
defined extra &
juxta foveal CNV
CNPVT(Choroidal
Neovascularization
Prevention Trial)
Prophylactic Rx of
large drusen for
prevention of
progression to wet
AMD in fellow eyes
of pts with CNV in 1
eye with low-
intensity laser
Laser Rx to high-
risk fellow eyes may
increase short-term
incidence of CNV
64. CLINICAL TRIALS FOR WET AMD
Name Aim & Methods Conclusion
CAPT
(Complication of
AMD Prevention
Trial)
Application of low
intensity laser in
eyes with drusen in
macula
Low intensity laser
Rx did not
demonstrate
a significant benefit
on vision in eyes of
people swith B/L
large drusen.
TAP (Treatment of
AMD with PDT)
To study the effect
of PDT on
subfoveal CNV
-PDT Rx significantly
reduces risk of loss
of 15 letters at 2
years
-The Rx was more
effective in classic
65. CLINICAL TRIALS FOR WET AMD
VISION (VEGF
Inhibition Study in
Ocular
Neovacularization)
Effect of 3 doses of
Macugen 0.3, 1 &
3mg, every 6 wks
evaluated in all sub
types of AMD
70% with 0.3
,65% with 1, 71%
with
3 mg showed loss
of less than 15
letters
66. Name Aim & Methods Conclusion
MARINA (Minimally
classic/occult trial of
the Anti-VEGF
Ab Ranibizumab In
treatment of
Neovascular AMD)
Pts received intravit
Ranibizumab (0.3
mg or 0.5mg) or
sham injections
once a month for 2
years.
-94.5% with 0.3 mg
and 94.6% with
0.5 mg lost < 15
letters as compared
to 62.2% in sham
group
-VA improved by 15
letters or more in
24.8% in 0.3mg
and 33.8% in 0.5
mg
67. Name Aim & Methods Conclusion
ANCHOR (Anti-
VEGF Ab for Rx of
Predominantly
Classic Choroidal
Neovascularization
in
AMD)
3 groups received
PDT & monthly inj.
-PDT + sham
-Sham PDT +
0.3mg Inj.
-Sham PDT + 0.5
mg
At 24 months less
than 15 letter loss
was seen in-
-90% of cases in
both the gps Rx
with Ranibizumab
Vs 64% in PDT only
gp
s-34% & 41% cases
in 0.3 & 0.5mg gp
showed
improvement of
>15 letters Vs 6%
in PDT group
68. Name Aim & Methods Conclusion
ProNTO
(Prospective
OCT Study With
Lucentis for
Neovascular AMD)
Pts received 3
consecutive
monthly inj of
0.5mg
Ranibizumab Pts
Monitored with
OCT & FFA
-Results were
comparable with
MARINA and
ANCHOR trials
-Avg of 9.9 inj
reqd as 25 with
monthly schedule
69. Name Aim & Methods Conclusion
PIER (Phase IIIb
Sham Injection-
Controlled Study of
efficacy & Safety of
Ranibizumab in
subfoveal CNVM
secondary to AMD)
Pt received 3 initial
monthly inj. of
Ranibizumab
followed by
quarterly inj. of
fixed regimen
The results were
poor in comparison
to MARINA &
ANCHOR
-Fixed regimen
can’t be used in
AMD to maintain
vision
70. Name Aim & Methods Conclusion
CATT (Comparison
of Age-related
Macular
Degeneration
Treatments Trials:
Lucentis-Avastin]
Evaluate relative
efficacy & safety of
treatment of
subfoveal, Wet AMD
with
-Lucentis on fixed
schedule,
-Avastin on fixed
schedule
-Lucentis on
variable
schedule
-Avastin on variable
schedule
Study going on
72. Pathogenesis
• The exact pathogenesis of mCNV is unknown, but elongation of axial
length and the changes associated with it should be the principal
cause.
• Disruption of the stretched Bruch’s membrane is suggested as one of
the mechanisms. In fact, the presence of lacquer cracks, which
represent breaks in the Bruch’s membrane, is associated with the
development of mCNV.
• Another hypothesis proposes the change in chorioidal circulation due
to the stretching of the Bruch’s membrane and choroid as a cause of
mCNV
73. • Diagnosis –
• mCNV is typically type 2 CNV and shows small grayish tissue on
funduscopy and slit-lamp biomicroscopy
• Fluorescein angiography (FA) generally shows classic CNV pattern,
• characterized by well circumscribed hyperfluorescence in the early
phase and active leakage in the late phase.
• Subretinal hemorrhage is commonly seen, but prominent pigment
epithelium detachment is rare
• high-to-moderate reflectivity above the RPE on optical coherence
tomography (OCT).
74. • In chronic stage, hyperfluorescent staining of the fibrous tissue with
minimal leakage is observed on FA.
• A well circumscribed, hyper reflective material is observed beneath
the retina on OCT.
75.
76.
77. Treatment
• Visual prognosis in mCNV is poor unless treated. It is reported that
visual acuity declines to <20/200 in 89% of the cases in 5 years and in
96% of the cases in 10 years.
• Laser photocoagulation
• PDT
• Anti- VEGF
• Surgical-
• Surgical removal of mCNV with or without macular translocation was
tried before the era of photodynamic therapy (PDT) and antivascular
endothelial growth factor (anti-VEGF) therapy.
79. • Inflammatory diseases comprise the second most common cause of
CNV in young patients
• The incidence of CNV is reported to be approximately 25% in patients
with posterior uveitis/panuveitis.
• Multiple evanescent white dot syndrome (MEWDS), punctate inner
choroidopathy (PIC), multifocal choroiditis (MFC, also known as MFC
with panuveitis), serpiginous choroiditis, VKH, Presumed ocular
histoplasmosis syndrome (POHS ) are the common causes
80. Pathogenesis
• The exact pathogenesis of inflammation-associated CNV is not
known. Upregulation of proangiogenic factors such as VEGF in case of
active inflammation would play a significant role in the etiology.
• Ischemia due to vasculitis can also induce VEGF upregulation.
• In case of infectious uveitis such as POHS or toxoplasmosis, immune
reaction to the pathogen is likely to be involved in the breakdown of
the Bruch’s membrane
81. Diagnosis
• CNV caused by inflammatory diseases is generally Gass type 2 and
shows a classic FA pattern.
• Abnormal findings such as drusen-like material, vitreous cells,
choroidal hyperreflectivity, and chorioretinal atrophy can be seen on
OCT.
