Myopic choroidal neovascularization:

Pathogenesis, epidemiology, and treatment

Dr. Elvioza SpM(K)

 Background

Pathological myopia (PM), also known as high, or

degenerative, or malignant myopia, is a leading
cause of visual loss, especially in younger
population (<50 years of age)1,2
PM is characterized by
 refractive error of at least −6 D1,3-5
 axial length ≥26 mm1,3-5
 degenerative changes involving the sclera, choroid,
and retina1,3-5
Myopic CNV is
 the most common vision-threatening complication
of PM2,6
 the leading cause of CNV second only to AMD2,6
AMD, age-related macular degeneration; 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525 5. Chan W-M, et al. Br J Ophthalmol 2005;89:1522-28
CNV, choroidal neovascularization; 2. Cohen SY, et al. Ophthalmology 1996;103:1241-44 6. Ohno-Matsui K, Yoshida K Curr Opin Ophthalmol
PM, pathological myopia 3. Fredrick DR Myopia BMJ 2002;324:1195-99 2004;15:197–202
4. Miller DG, Singerman LJ, Curr Opin Ophthalmol 2001;12:222-224 2
 Risk factors associated with development of
myopic CNV

 Older patients with PM have a higher risk of developing CNV,

Age which may be due to dysfunction in the retinal pigment
epithelium/choroidal circulation1,2

 Predominant in females2,3
Gender  Possible role of estrogen receptor expression in CNV

 Eyes disorders that may contribute to the development of

myopic CNV:2,4-6
Disorders
of eye
CNV, choroidal neovascularization
PM, pathological myopia
RPE, retinal pigment epithelium
 High myopia
 Myopic CNV in fellow eye
 Choroidal thinning due to the increased RPE/choroid curvature
 Lacquer cracks/patchy atrophy
 Choroidal filling delay
1. Shih Y-F, et al. Br J Ophthalmol 2006;90:546-50 4. Ohno-Matsui K, et al. Br J Ophthalmol 2003 87:570-73
2. Silva R Ophthalmologica 2012;228:197-213 5. Ikuno Y, et al. Invest Ophthalmol Vis Sci 2010;51:3721-25
3. Kobayashi K, et al. Retina 2002;22:418-22 6. Wakabayashi T and Ikuno Y Br J Ophthalmol 2010;94:611-15
3
 Risk factors associated with development of
myopic CNV (cont’d)

Geographical
 Higher prevalence of PM in Asian population1
location

 Genes for high myopia (nonsyndromic high myopia)1,2

 Several genetic loci such as 2q37.1 (MYP12), 4q22–27 (MYP11) and
Genetic 7q36 (MYP4) are linked to high myopia
factors  Possible relation of complement factor I (CFI) gene to myopic
CNV 3

 Factors that may increase the risk of high myopia, that may
Environmental further lead to CNV are:1,2
factors  Increased IOP
 Higher level of near-work activities

CNV, choroidal neovascularization; 1. Silva R Ophthalmologica 2012;228:197-213

IOP, intraocular pressure; 2. Young TL Trans Am Ophthalmol Soc 2004;102:423-46
RPE, retinal pigment epithelium 3. Leveziel N, et al Invest Ophthalmol Vis Sci 2012;53:5004-09
4
 Pathogenesis of myopic CNV

The pathogenesis of myopic CNV remains unclear

Several theories have been proposed for pathogenesis of myopic CNV:
1. Mechanical theory
2. Heredo-degenerative theory
3. Hemodynamic changes in choroidal circulation
 Mechanical theory1-4
Progressive and excessive elongation of the
anteroposterior axis Lacquer cracks

Formation of lacquer cracks

Imbalance between angiogenic factors

(VEGF) and anti-angiogenic factors (PEDF)
Development of myopic CNV
CNV, choroidal neovascularization;
PEDF, pigment epithelial derived growth factor;
VEGF, vascular endothelial growth factor
Myopic CNV
1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
2. Ohno-Matsui K, et al. Br J Ophthalmol 2003 87:570-73
3. Tong J-P, et al. Am J Ophthalmol 2006;141:456-62
4. Kim YM, et al. Eye 2011;25:937-46 5
 Pathogenesis of myopic CNV (cont’d)

 Heredo-degenerative theory1-4
 Myopic CNV may be related to genetic processes associated with PM

 Hemodynamic changes in choroidal circulation1,3,5,6

 Choroidal filling delay at the macular area and diffuse thinning of the choroid
are the two hemodynamic factors associated with myopic CNV
 These hemodynamic changes lead to decrease in choroidal perfusion
resulting in choroidal ischemia along with subsequent up regulation of
angiogenic factors and development of CNV

CNV, choroidal neovascularization 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525 4. Young TL Trans Am Ophthalmol Soc 2004;102:423-45
PM, pathological myopia 2. Leveziel N, et al. Invest Ophthalmol Vis Sci 2012;53:5004-09 5. Wakabayashi T, Ikuno Y Br J Ophthalmol 2010;94:611-15
3. Ikuno Y, et al. Invest Ophthalmol Vis Sci 2010;51:3721–25 6. Grossniklaus HE, Green WR Retina 1992;12:127-33
6
 Symptoms of myopic CNV

Patients with myopic CNV may

present one or more of the
following symptoms:1-4
 Acute decrease in vision
 Metamorphopsia
Decrease in vision Metamorphopsia
 Scotoma (visual field defects)
 Flashes of light or floaters

Scotoma Floaters

CNV, choroidal neovascularization 1. Virgili G, Menchini F Cochrane Database Syst Rev 2005;4:CD004765
2. www.aoa.org/documents/CPG-15.pdf (Accessed on Sept 1 2012)
3. www.aoa.org/documents/QRG-15.pdf(Accessed on Sept 1 2012)
4. Soubrane G Surv Ophthalmol 2008;53:121-38 7
 Diagnosis of myopic CNV

Various techniques used for the diagnosis of myopic CNV include:1,2

Fluorescein angiography

Indocyanine green angiography

Optical coherence tomography

Fundus autofluorescence

CNV, choroidal neovascularization 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
2. Silva R Ophthalmologica 2012;228:197-213

8
 Diagnosis of myopic CNV (cont’d)

Fluorescein angiography (FA)1-3

 Provides information about
► presence, type, and activity of myopic CNV
► location of CNV with respect to the fovea
 Useful in differentiating macular and subretinal
FA image showing
hemorrhage myopic CNV

 Helps in decision making process for treatment and

retreatment
Limitation:
 Difficulty in identifying the fovea in eyes with PM

CNV, choroidal neovascularization; 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
PM, pathological myopia 2. Barbazetto I, et al. Arch Ophthalmol 2003;121:1253-68
3. Parodi MB, et al. Br J Ophthalmol 2003;87:177-83
9
 Diagnosis of myopic CNV (cont’d)

Indocyanine green angiography (ICGA)1,2

 Adjunctive to FA in the diagnosis of myopic CNV
 Allows to observe lacquer cracks, choroidal atrophy, any
dark rim, and late-phase hyperfluorescence
 Provides a better understanding of choroidal circulation
ICGA image shows
 ICGA not impaired due to blood, pigments, and exudates hyperfluorscent
choroidal vein in
eye with myopic CNV
Limitation:
 Alteration of choriocapillaris may affect the choroidal
circulation and also the permeability to ICG molecules

CNV, choroidal neovascularization; 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
FA, fluorescein angiography; 2. Kim YM, et al. Eye (Lond) 2011;25:937-46
ICG, indocyanine green
10
 Diagnosis of myopic CNV (cont’d)

Optical coherence tomography (OCT)1,2

 Useful in evaluating the stage and activity of myopic CNV
 Helps to identify co-existing pathologies related to myopia,
such as epiretinal membrane and retinoschisis
 A vital tool for the assessment of retinal thickness and
differentiating myopic CNV from CNV due to AMD
OCT B-scan image of an
 Active myopic CNV is observed as a highly reflective, dome- eye with myopic CNV

like elevation above the RPE

Limitations:
 Cannot differentiate blood from fibrosis on CNV
 May need biomicroscopy/fundus angiography to establish
the diagnosis of myopic CNV
AMD, age-related macular degeneration; 1. Baba T, et al. Acta Ophthalmol Scand 2002;80:82-7
CNV, choroidal neovascularization; 2. García-Layana A, et al. Br J Ophthalmol 2006;90:555-58
RPE, retinal pigment epithelium
11
 Diagnosis of myopic CNV (cont’d)

Fundus autofluorescence (FAF)1,2

 Allows visualization of accumulated lipofuscin within the
functional RPE in vivo
 Eyes with myopic CNV show area of relative
hypoautofluorescence
 Myopic CNV exhibits a specific, high signal, FAF pattern FAF image of subfoveal
myopic CNV
 Helps in the qualitative and quantitative assessment of the
progression or severity of chorioretinal atrophy secondary
to CNV

CNV, choroidal neovascularization; 1. Sawa M, et al. Br J Ophthalmol 2008;92:1236-40

RPE, retinal pigment epithelium 2. Parodi MB, et al. Br J Ophthalmol 2009;93:6771-74

13
 Current treatment options

Currently used therapeutic modalities include:

Medical1,2 Surgical1,2

Laser Surgical excision/

photocoagulation removal of CNV

Macular/foveal
Verteporfin PDT
translocation surgery

Anti-VEGF agents*

*Off label/investigational use 1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
CNV, choroidal neovascularization; 2. Silva R Ophthalmologica 2012;228:197-213
PDT, photodynamic therapy;
VEGF, vascular endothelial growth factor 14
 Current treatment options (cont’d)

Laser photocoagulation1-3
 Laser photocoagulation has been widely used to treat extrafoveal myopic
CNV though the level of evidence on its benefit is not high1-3
 It may reduce/prevent further VA loss by preventing the extension of
neovascular lesion to the center of the fovea
 Limitations:
► May damage retinal tissues, hence not a choice for treating juxtafoveal and
subfoveal CNV
► Good visual acuity cannot be maintained over long-term
► Recurrence of CNV (31% to 72%)
► May cause permanent chorioretinal scars or scotomas
► Laser scar expansion (laser creep) may cause complications and lead to
loss of central vision
CNV, choroidal neovascularization; 1. Virgili G, Menchini F Cochrane Database Syst Rev 2005;4:Art. No.:CD004765
VA, visual acuity 2. Ruiz-Moreno JM, Montero JA Eur J Ophthalmol 2002; 12:117-22
3. Tano Y, Am J Ophthalmol 2002;134:645-60
15
 Current treatment options (cont’d)

Verteporfin (Visudyne®, Novartis Pharma AG, Basel, Switzerland) PDT1-3

 vPDT is the only approved treatment for subfoveal myopic CNV
 May be considered as a potential alternative in treating juxtafoveal lesions
 Results from the VIP study demonstrate a visual benefit for vPDT compared
with placebo therapy through 2 years of follow-up
 It may delay further VA deterioration and help to retain central vision
 Limitations:
► Patients may have visual loss due to persistent leakage from the CNV
► vPDT has angio-occlusive property and does not control the disease activity
(angiogenesis/neovascularization)
► PDT may induce chorioretinal damage in some patients

CNV, choroidal neovascularization;

PDT, photodynamic therapy; 1. Verteporfin in Photodynamic Therapy Study Group Ophthalmology 2001;108:841-52
VIP, Verteporfin in Photodynamic Therapy; 2. Blinder KJ, Ophthalmology. 2003;110:667-73
vPDT, verteporfin photodynamic therapy; 3. Pece A, et al. Ophthalmologica 2011;225:161-68
VA, visual acuity 16
 Current treatment options (cont’d)

Surgical approaches for myopic CNV include

- surgical excision of CNV
- macular translocation1-6

 With the advent of newer and less invasive treatment modalities, such as
PDT and VEGF inhibitors, surgical excision of myopic CNV is no longer a
viable option for a majority of patients with myopic CNV
 Advanced techniques such as modified and extended macular translocation
surgery have the potential to preserve central vision
 Potentially useful in CNV cases with foveal fibrosis or in eyes that are
non-responsive to laser/PDT/anti-VEGFs

CNV, choroidal neovascularization;
PDT, photodynamic therapy;
RPE, retinal pigment epithelium
VEGF, vascular endothelial growth factor
1. Ruiz-Moreno JM, de la Vega C Br J Ophthalmol 2001;85:1041-43 4. Yamada Y, et al. Am J Ophthalmol 2010;149:453-57
2. Uemura A, Thomas MA Arch Ophthalmol 2000;118:344–50 5. Fujii GY, et al. Am J Ophthalmol 2001;131:90-100
3. Cekic O, et al. Ophthalmology 2000;107:2117 6. Kumari N, et al. Prog Retin Eye Res 2012;31:495-525
17
 Anti-VEGFs for the treatment of myopic CNV

Increased VEGF levels found in

myopic CNV and other conditions1 Intravitreal anti-VEGF

Increased VEGF
levels Decreased Increased
VEGF levels2 PEDF levels2

Diffusion
Preliminary clinical
experience

Rapid and sustained

improvement in vision3–6

Anti-VEGF agents currently being evaluated for use in myopic CNV

Agent Manufacturer Status of use
Lucentis® (ranibizumab) Novartis Investigational7
Eylea® (aflibercept) Regeneron/Bayer Investigational8
Avastin® (bevacizumab) Genentech/Roche Off-label
CNV, choroidal neovascularization; 1. Tong JP, et al. Am J Ophthalmol 2006;141:456-62 5. Calvo-Gonzalez C, et al. Am J Ophthalmol 2011;151:529-34
PEDF, pigment epithelium-derived factor; 2. Chan WM, et al. Retina 2008;28:1308-13 6. Yoon JU, et al. Retina 2010;30:418-24
VEGF, vascular endothelial growth factor 3. Ikuno Y, et al. Am J Ophthalmol 2009;147:94-100 7. www.clinicaltrials.gov (NCT01217944)
4. Ruiz-Moreno JM, et al. Retina 2010;30:1609-15 8. www.clinicaltrials.gov (NCT01249664) 18
 Anti-VEGFs for the treatment of myopic CNV:
Ranibizumab
Ranibizumab is a humanized, monoclonal antibody fragment (Fab),
specifically designed for ocular use, that selectively binds to and inhibits
all active isoforms of VEGF-A1,2
Based on well established efficacy and safety profile in wet AMD, visual
impairment due to DME or RVO, ranibizumab is approved in more than
100 countries for wet AMD and more than 80 countries for DME and RVO3
Recent preliminary clinical trials with ranibizumab have demonstrated
promising results for the treatment of myopic CNV with a low number of
injections4-7
The recently completed pivotal trial RADIANCE (NCT01217944), comparing
ranibizumab versus vPDT, provides important, high level evidence of the
benefits of ranibizumab for the treatment of myopic CNV8-10
AMD, age-related macular degenration;
CNV, choroidal neovascularization;
DME, diabetic macular edema; 1. Jager RD et al. N Engl J Med 2008;358:2606-17 6. Calvo-Gonzalez C, et al. Am J Ophthalmol 2011;151:529-34
RCT, randomized clinical trial; 2. Ferrara N et al. Retina 2006;26:859-70 7. Vadalà M, et al. Br J Ophthalmol 2011;95:657-61
RVO, retinal vein occlusion; 3. Novartis Pharma AG. Lucentis® SmPC. 2012 (EMA) 8. www.clinicaltrials.gov (NCT01217944)
VEGF, vascular endothelial growth factor; 4. Mones JM, et al. Eye (Lond). 2009;23:1275-80 9. 5. Wolf S on behalf of the study group, APAO, 2013
vPDT, verteporfin photodynamic therapy 5. Silva RM, et al. Retina 2010;30:407–12 10. Novartis data on file 19
 Anti-VEGFs for the treatment of myopic CNV:
Ranibizumab (cont’d)
 Summary of key outcomes from some retrospective studies
Number of
No. of Duration of
Study ranibizumab Study outcomes
patients follow-up
injections (mean)
Mean BCVA gain: +14.1 letters in patients
Yoon et al. 2010 treated with anti-VEGF at month 12
128* 36 months Year 1: 1.6
(Korea)1 BCVA improvement ≥15 letters:
39.7% of the patients
Mean BCVA: +15 letters§
Lai 2012
15 24 months 3.8 BCVA improvement ≥15 letters:
(China)2
73.3% of the patients
Mean BCVA gain:# +4.3 letters at
Franqueira 12 months, +6.4 letters at 24 months and
Year 1: 4.1
2012 +8 letters at 36 months
39 36 months Year 2: 2.4
(Portugal)3 BCVA improvement ≥15 letters:
Year 3: 1.1
25% (12 months), 30% (24 months) and
35% (36 months) of the patients

*39 patients were treated with anti-VEGF agents

§logMAR BCVA change from 0.86 to 0.53 1. Yoon JU, et al. Retina 2010;30:418-24
#calculated from baseline and outcome data 2. Lai TY, et al. Eye (Lond) 2012;26:1004-11
BCVA, best-corrected visual acuity; 3. Franqueira N, et al. Ophthalmologica 2012;227:39-44I
CNV, choroidal neovascularization 20
 Anti-VEGFs for the treatment of myopic CNV:
Ranibizumab (cont’d)
 Summary of key outcomes from some prospective studies
Number of
No. of Duration of
Study ranibizumab Study outcomes
patients follow-up
injections (mean)
Mean BCVA gain: +9.5 letters
Monés 2009
23 12 months 1.5 BCVA improvement ≥15 letters:
(Spain)1
27% of the patients
Mean BCVA gain: +8 letters (12 months)
Silva 2010
32 ≥12 months 3.6 BCVA improvement ≥15 letters: 24% of
(Portugal)2
the patients
Mean BCVA gain: +12 letters at end of
Calvo-Gonzalez 15.9 months follow-up;
67 4.2
2011 (Spain)3 (mean) BCVA improvement ≥15 letters:
40% of the patients
Mean BCVA gain: Mean VA increased
from 20/131 to 20/42 (approximate BCVA
Vadalà 2011 13.3 months
39 2.8 gain +10 letters)
(Italy)4 (median)
BCVA improvement ≥15 letters:
59% of the patients
BCVA, best-corrected visual acuity; 1. Mones JM, et al. Eye (Lond) 2009;23:1275-80
CNV, choroidal neovascularization; 2. Silva RM, et al. Retina 2010;30:407–12
VA, visual acuity 3. Calvo-Gonzalez C, et al. Am J Ophthalmol 2011;151:529-34
4. Vadalà M, et al. Br J Ophthalmol 2011;95:657-61 21
 Anti-VEGFs for the treatment of myopic CNV:
Ranibizumab (cont’d)
 Summary of key outcomes from some recently completed studies
Treatment regimen
No. of Description of
Study [Mean number of Study outcomes
patients study
injections]
12 month, phase II, Primary endpoint:
open‐label, single- Ranibizumab 0.5 mg Mean change in BCVA over 12 months
REPAIR1-3 48
arm multicenter, PRN [3.6] Results:
UK based study Mean BCVA gain: +13.76 letters

Primary endpoint:
Group I: Ranibizumab Mean average change in BCVA from
0.5 mg (BCVA stability baseline to Month 1 through Month 3
12 month, phase III,
based) [4.6] Results:
randomized,
RADIANCE4-6 Group II: Ranibizumab VA gains in the ranibizumab groups
275 double-masked,
0.5 mg (disease activity were maintained at Month 12
multicenter, active-
based) [3.5] Mean average change in BCVA from
controlled study
Group III: baseline to Month 1 through Month 3:
Verteporfin PDT [3.2] Group I: 10.5 letters, Group II :10.6
letters, and Group III: 2.2 letters

BCVA, best-corrected visual acuity; 1. www.clinicaltrials.gov; (NCT01037348) 4. www.clinicaltrials.gov; (NCT01217944)

CNV, choroidal neovascularization; 2. Tufail A, et al. ARVO, 2012 5. Wolf S on behalf of the study group, APAO, 2013
PDT, photodynamic therapy 3. Novartis data on file 6. Novartis data on file
22
 Anti-VEGFs for the treatment of myopic CNV:
Bevacizumab
Bevacizumab is a full-length monoclonal antibody that binds and inhibits
all isoforms of VEGF A1
Several preliminary clinical trials with intravitreal bevacizumab have
reported positive visual and anatomical outcomes in patients with
myopic CNV2-5
Limitations:
 Bevacizumab is not approved for ophthalmic use
 Optimal dose and treatment interval are not established4
 Efficacy and safety profile not established (large RCTs lacking)

CNV, choroidal neovascularization; 1. Ng DS, et al. Clin Experiment Ophthalmol 2012;40:e98-e110 4. Ikuno Y, et al. Am J Ophthalmol 2009 ;147:94-100
RCT, randomized clinical trial; 2. Chan WM, et al. Br J Ophthalmol 2009;93:150-54 5. Nakanishi H, et al. Eye 2011;25:375-81
VEGF, vascular endothelial growth factor 3. Ruiz-Moreno JM, et al. Retina 2010;30:1609-15
23
 Anti-VEGFs for the treatment of myopic CNV:
Bevacizumab (cont’d)
 Summary of key outcomes from some prospective and retrospective studies
No. of Duration of Number of Study outcomes
Study
patients follow-up injections (mean) (BCVA, logMAR units)
Prospective studies
Mean BCVA improved from 0.62 to 0.38
Chan et al. 20091 29 12 months 3.6 at 12 months
(approximate BCVA gain +10 letters)
Mean BCVA improved from 0.72 to 0.53
Ruiz-Moreno and
107 12 months 1* at 12 months
Montero, 20102
(approximate BCVA gain +10 letters)
Retrospective studies
Mean BCVA improved from 0.57 to 0.33
Ikuno et al. 20093 63 12 months 2.4 at 12 months
(approximate BCVA gain ≥+10 letters)
Mean BCVA improved from 0.74 to 0.46
Nakanishi et al.
23 24 months 1.4 at 24 months
20114
(approximate BCVA gain ≥+10 letters)
*For 60% patients 1. Chan WM, et al. Br J Ophthalmol 2009;93:150-54
BCVA, best-corrected visual acuity; 2. Ruiz-Moreno JM, et al. Retina 2010;30:1609-15
CNV, choroidal neovascularization 3. Ikuno Y, et al. Am J Ophthalmol 2009 ;147:94-100
4. Nakanishi H, et al. Eye 2011;25:375-81 24
Aflbercept

25
 MYRROR: Dosing schedule

▪ Phase III trial to assess the efficacy, safety and tolerability of

intravitreal aflibercept for the treatment of myopic CNV
in an Asian population of 122 subjects

Aflibercept group

Sham/ Aflibercept
group

Sham/ Aflibercept group: Sham incl. Week 20

Sham/ Aflibercept group first injection at week 24

IVT-AFL: intravitreal aflibercept.

Ikuno Y. et al . 2015 . Ophthalmology Volume 122, Number 6,; 1221-1227

26
 A limited number of injections was needed

Ikuno Y. et al . 2015 . Ophthalmology Volume 122, Number 6,; 1221-1227

27
MYRROR: Mean change in BCVA from baseline to week 24
and 48 (full analysis set)

Week 24 Week 48 Week 48

Week 48
Treatment n Baseline Mean Week 48 Mean LS Mean
Diff. (95% CI)
P value
Change Change Change

Arrow indicates the time of first mandatory active injection in the delayed treatment group.
LS: least squares.
Ikuno Y. et al . 2015 . Ophthalmology Volume 122, Number 6,; 1221-1227 28
 MYRROR: Changes in central retinal thickness (CRT)
from baseline to week 48 (data as observed)

Arrow indicates the time of first mandatory active injection in the delayed treatment group.
FU: Follow-up.
Ikuno Y. et al . 2015 . Ophthalmology Volume 122, Number 6,; 1221-1227 29
 Summary

 Myopic CNV is the most common vision-threatening complication of

PM and is the leading cause of CNV in younger patients (<50 years)1,2
 Various risk factors like age, gender, genetics, and environment seem
to be associated with the development of myopic CNV1,2
 Combination of one or more diagnostic techniques such as FFA, ICGA,
and OCT can confirm the presence of myopic CNV1,2
 Laser photocoagulation and vPDT stabilize but rarely improve vision
and may not control the disease activity (neovascularization)1
 Anti-VEGF therapies show promising results, and may provide rapid and
sustained visual improvement in patients with myopic CNV1-3

CNV, choroidal neovascularization;

FFA, fundus fluorescein angiography;
1. Neelam K, et al. Prog Retin Eye Res 2012;31:495-525
ICGA, indocyanine green angiography;
2. Silva R Ophthalmologica 2012;228:197-213
OCT, optical coherence tomography;
PM, pathological myopia
vPDT, verteporfin photodynamic therapy 30