A presentation prepared by: Dr Robin Goh Chon Han Ophthalmology Postgraduate Master Student University Malaya Malaysia 16.04.2022

1. Polypoidal
Choroidal
Vasculopathy
Prepared by
Dr Robin Goh Chon Han
Postgraduate Ophthalmology Master Student
University Malaya Malaysia
2022

2. Case Senarios
Miss H
49 yo / Malay / Lady
U/L :
1) Hypertension x 10 years
C/O:
RE Painless Gradual BOV x 1/12
progressively worsening

3. VA
RE 6/12, Ph 6/12
LE 6/6, Ph 6/6
RAPD -ve
BE Anterior Segments were normal

4. + small (1/5 DD) subfoveal
orange nodular lesion with
minimal surrounding
subretinal hemorrhage
+ 4DD of macular
hyperpigmented RPE
changes surrounding the
orange nodule (requiring
stereoscopic view to identify
presence of macular swelling)
NO DRUSENS
NO MYOPIC CHANGES
NO ANGOID STREAK
NO HPT/DR Changes
Clear media

5. Flat macula with good foveal reflex
No macular drusen
No macular scarring

6. What are the differential diagnoses?
• RE PCV
• RE nAMD
• RE Myopic CNV
• RE Chronic CSR with CNV (PNV)

7. Any other relevant history to enquire?
üHOPI
§ It is a second attack
§ Claimed had history of RE sudden reduced of vision 2 years ago
§ Visited ophthalmologist @ Government Hospital
§ Given intravitreal injections x 3 for “right eye retinal lesion with retinal bleeding”
§ Vision recovered fully and defaulted subsequent f/up
§ no ocular trauma
üPast ocular history
§ Patient claims was wearing spectacles since secondary school
§ (BE power -5.0D)
§ BE vision was perfect

8. üPast Medical History
• Hypertension
• BMI = 30
ü Family history
§ unremarkable
ü Social history
• Working as sales executive
• husband is an active smoker who smokes at home

9. What further ocular investigations to perform?
Spectrum domain OCT
- at fovea cut
- Multiple PED
- Notched PED

10. Spectrum domain OCT
- at location superior
temporal of the macula
- Multiple PED
- Notched PED
- Subtle hyperreflective
rings with internal
hyporeflective lumen

11. RE FAF
- Multiple hyperautofluoroscence foci at
the region of suspicious lesion (sick RPE)
- Area of hypoautofluoroscence
(possible RPE atrophy)

12. FFA
Foci of stippled
hyperfluoroscence
(increased in intensity
and slight increased
with size with not well
defined border)
[ Type 1 CNV ]

13. RE ICG
Early choroidal hypercyanescence at location corresponds to orange nodule
hypocyanescence halo
pulsative filling
BVN

14. Diagnosis?
• RE Polypoidal Choroidal Vasculopathy

15. PCV Prevalence
• Accurate prevalence rate = unclear
• 0.5% of general population (Northern China) (1)
• 4 to 13.9% in white patients presented with nARMD (2)
• 22.3 to 61.6% in Asian patients presented with nARMD (2)
• More prevalent in Asians
• Commonly affecting Asian Men & Caucasian women
• Generally younger age of onset and unilateral disease
compared to ARMD
(1) Li Y, You QS, Wei WB, et al. Polypoidal choroidal vasculopathy in adult chinese: the Beijing Eye Study. Ophthalmology. 2014;121:2290–2291.
(2) Palkar AH, Khetan V. Polypoidal choroidal vasculopathy: An update on current management and review of literature. Taiwan J Ophthalmol
2019;9:72-92.

16. PCV Risk Factors
•Cigarette smoking (4 fold risk) (1)
• High BMI
• High Cholesterol
• Coronary Artery Disease
• Inflammatory Markers (CRP, IP-10, Homocysteine) (2)
• Genetics (Complement Factor H, ARMS2, CETP,HTRA1,
CFB, RDBP, SKIV2L, 4q12, 8p21) (2)
(1) Cackett P, Yeo I, Cheung CM, Vithana EN, Wong D, Tay WT, et al. Relationship of smoking and cardiovascular risk factors with
polypoidal choroidal vasculopathy and age‑ related macular degeneration in Chinese persons. Ophthalmology 2011;118:846‑ 52.
(2) Palkar AH, Khetan V. Polypoidal choroidal vasculopathy: An update on current management and review of literature. Taiwan J
Ophthalmol 2019;9:72-92.

17. Pathophysiology of PCV

18. Etiology of PCV
•Idiopathic
• Exact etiology = poorly understood
? Choroidal vasculature dilation & aneurysmal formation
? Abnormal choroidal blood vessel (intraBM or Choroid)
? Variable VEGF expression in RPE and vascular endothelium

19. Possible inter-relationship of:
PACHYCHOROID TYPE 1 CNV PCV

20. Pachychoroid
• characterized by attenuation of
choriocapillaries overlying dilated choroidal
veins
• associated with
choroidal thickening,
choroidal hyperpermeability,
progressive RPE dysfunction
& subsequent neovascularization
Pachychoroid Disease Spectrum
• Central serous retinopathy (CSR)
• Pachychoroid pigment epitheliopathy (PPE)
• Pachychoroid neovasculopathy
• Polypoidal Choroidal Vasculopathy (PCV)
• Peripapillary Pachychoroid Syndrome
• Focal Choroidal Excavation

21. Fluid overload
overcomed by RPE
Fluid overload unable
to overcome by RPE
Microrip in BM
*** Vessels forming
terminal polyps --> PCV

22. Type 1 CNV
• Pathological new blood vessels growing from
choriocapillaries
• due to elevated proinflammatory cytokines (IL-1Beta, IL-23)
• Invading subRPE
• Abnormal vascularization (forming polyps and BVN)
• Capillary like vessels leakage of plasma or blood (Exudation)
+/- fibrovascular scar tissue formation

23. EVEREST Trial diagnostic criteria for PCV
• Early subretinal ICG hyperfluorescence (first 5mins)
[ + at least 1 out of 6 ]
1. Nodular (elevated) appearence of polyp on stereoscopic viewing
2. Orange subretinal nodules at the area of hyperfluorescent
3. Hypofluorescent halo around nodule
4. BVN on ICG
5. Pulsatile filling of polyps on dynamic ICG
6. Massive submacular hemorrhage (>4 DD)

24. Example

25. FFA
Test yourself.

26. NON ICGA Diagnostic Criteria for PCV
• OCT Features:
Sharp peaked PED
Sub RPE ring like lesion
Complex RPE elevation (En face OCT)
Double layer signs
Thick choroid with dilated Haller’s layer vessels
Predominantly SRF
According to Asia-Pacific Ocular
Imaging Society PCV Workgroup
- Achieving diagnostic accuracy of 82%
Cheung CMG, Lai TYY, Teo K, et al. Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph
Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. Ophthalmology. 2021 Mar;128(3):443-452. doi:
10.1016/j.ophtha.2020.08.006. Epub 2020 Aug 11. PMID: 32795496.

27. Example

28. + Multiple PED,
+ Notched PED notch
+ Sharp PED peak (arrowhead) corresponding to
the polyp

29. + Notched PED (black arrow),
+ Double-layer sign (black arrowhead)
+ Hyperreflective rings with internal
hyporeflective lumen (white arrow).

30. Management for the case
• Previous record traced
• RE IVT Ranibizumab given x 3 in 2019
Ø RE IVT Aflibercept given x 3
@ 02/12/2021
@ 13/01/2022
@ 30/03/2022
Reduced in PED height
Reduced CMT
Vision improved to 6/9

31. General Treatment options
• Thermal laser photocoagulation
• PDT
• AntiVEGF
• Combination

32. General Treatment Algorithm
• If VA 6/9 or better: Observation or IVT Anti-VEGF if noted significant exudate
• If VA 6/12 or worse: Treatment for symptomatic patients
• PDT = effective initial treatment if available
• PDT + IVT AntiVEGF = If the polypoidal lesion is associated with significant
exudate or fluid
• Repeat IVT AntiVEGF = for Recurrent associated fluid that is visually significant
and responsive to anti-VEGF intravitreal injection to maintain stable vision
• Switch to different agent = If lesions are not responsive to repeat injections
• Laser photocoagulation of extrafovea polypoidal lesions if PDT not available

33. Summary of Landmark studies for PCV
Study Design Results
LAPTOP Prospective, Multicenter RCT
2 Arms:
(1) PDT monotherapy
(2) IVT Ranibizumab 0.5mg x 3 then PRN
IVT Ranibizumab group gained
higher 0.2 logMAR at 1 year, 2 years
and 5 years (30.4% vs 17%)
IVT Ranibizumab better than PDT
monotherapy
EVEREST Prospective, Multicenter RCT
3 Arms:
(1) PDT + IVT Ranibizumab 0.5mg x3
(2) IVT Ranibizumab 0.5mg monotherapy x3
(3) PDT monotherapy
Combination PDT + IVT
Ranibizumab yielding best results
(77.8% complete polyp regression
vs 71.4% in PDT vs 28.6% in IVT
Rani)

34. Study Design Results
EPIC Open-label clinical trial
(1) IVT Aflibercept 2mg for active disease x 3
monthly loading then 2 monthly maintainence for 2
years
* previously treated and treatment naive patients
72% SRF resolution, 75% subretinal
hemorrhage resolution, 87% PED
improvement with IVT Aflibercept
IVT Aflibercept is effective for PCV
lesion failed IVT Raibizumab or
Bevacizumab
PLANET Prospective, sham controlled RCT
(1) IVT Aflibercept 2mg monthly x 3 + sham
(2) IVT Aflibercept 2mg monthly x 3 + rescue PDT
116 (81.7%) and 136 (88.9%),
respectively, had no polypoidal
lesions with leakage.
IVT Aflibercept monotherapy is
not inferior to combination with
PDT

35. Other agent
• Bevacizumab (Avastin) :
off label use, low complete polyp regression rate, low cost
• Ziv-aflibercept (Zaltrap) :
antiVEGF approved for metastatic colon cancer. off label use for nARMD and PCV. Noted
improvement in PCV cases refractory to other antiVEGF at 9-months. Long term efficacy yet to
determined.
• Convercept (Lumitin) : PANDA-1 & PANDA-2 trials
fusion protein that inhibits VEGF-A, VEGF-B and PIGF.
approved in China for neovascular ARMD
0.5mg or 2.0mg no difference. effective.

36. Prognosis

37. Prognosis
• 50 % spontaneous resolution of exudation and hemorrhage
• Thicker subfoveal choroidal thickness = less responsive to antiVEGF
monotherapy
• Recurrence rate = 50% after 18months

38. Reference
• Chui Ming, Gemmy Cheung et al. Polypoidal choroidal vasculopathy, Definition,
Pathogenesis, Diagnosis & Management. AAO
https://www.aaojournal.org/article/S0161-6420(17)32863-4/fulltext
• Christine P S Ho et
://www.ijo.in/article.asp?issn=0301-
4738;year=2018;volume=66;issue=12;spage=1727;epage=1735;aulast=Ho#ft82
• Mark O.M Tso et al. Pathologic study of early manifestations of polypoidal choroidal
vasculopathy and pathogenesis of choroidal neovascularization. American Journal of
Ophthalmology case reports. Volume 11, Sep 2018, Page 176-180
https://www.sciencedirect.com/science/article/pii/S2451993616302158