1. 가톨릭대학교 의과대학 안과 및 시과학 교실 R3 장동진 / Pf.이원기
Efficacy of Intravitreal Bevacizumab Combined With Photodynamic Therapy for Polypoidal Choroidal Vasculopathy
Am J Ophthalmol 2010;150:48-54 e1.
가톨릭대학교 의과대학 안과 및 시과학 교실
R3 장동진 / Pf.이원기

2. Introduction Polypoidal choroidal vasculopathy (PCV)
complex of branching vascular networks terminating in aneurysmal or polypoidal lesions.
higher in Asian
accounts for almost half of eyes presumed to have exudative age-related macular degeneration (AMD) in Japan

3. Introduction Photodynamic therapy (PDT) with verteporfin (Visudyne)
subfoveal choroidal neovascularization (CNV) associated with AMD
effective for treating PCV
unexpected subretinal hemorrhages after PDT
Bevacizumab (Avastin)
For treating CNV secondary to AMD
the efficacy for PCV seems limited
reduced exudative fluid but did not affect the original abnormal vasculatures
 subsequent recurrence of fluid in most eyes.

4. Introduction Combination?
PDT - occlusion of polypoidal vascular lesions
anti-VEGF drugs - resolution of the associated fluid
but some limitations
Combination?

5. Methods 146 Japanese patients
Diagnosed based on indocyanine green angiography (ICGA).
Symptomatic, treatment-naïve, subfoveal PCV
Retrospective, comparative, interventional case series
PDT
1.25mg bevacizumab
1 day before PDT
1, 3, 6, 9, 12 month
Comprehensive ocular exam.
(including BCVA, Fundus exam,
color fundus photography, OCT
FAG, ICG baseline and every 3months
Additional intermediate visits at 4- to 6-week intervals
Additional treatments
Abnormal vascular lesion  PDT
Exudative fluid on OCT  Bevacizumab inj.(combined tx group only)

6. Methods “Resolution” of PCV lesions after the initial treatment
disappearance of symptomatic vasculatures on ICGA at 3 months with complete resolution of exudative fluid on OCT
“Recurrence”
reappearance of abnormal vasculature on ICGA with exudative fluid on OCT.

7. Results

8. Results
* : P<0.05 $ $ $ $ % % $ %

9. Results Improved or maintained BCVA Improved BCVA 61/61 81/85
61/ /85
55/ /85
100% %
90.2% %
14.8% 3.5%
23.0% 18.8%
Improved or maintained BCVA
Improved BCVA
62.3% 54.1%

10. Results Factors associated with the long-term BCVA
multivariate analyses
baseline BCVA (P < )
the GLD (P = )
PED (P = )
treatment (P = 0.048)
BCVA
at 12 months
better baseline VA
smaller lesion size
absence of PED
combined therapy

11. Results Monotherapy Combination Therapy p
Resolution of lesions at 3 months
75.3% (64/85)
78.7% (48/61)
0.63
Recurrence
40.6% (26/64)
43.8% (21/48)
0.74
Additional treatments
during the 1-year follow-up
0.66 PDT
0.43 PDT,
0.92 bevacizumab additional injections
Pearson chi-square test

12. Results Adverse events within a month Monotherapy Combination Therapy
a subretinal or subpigment epithelial hemorrhage, or both
>1mm
15 eyes (17.7%)
3 eyes (4.9%)
0.022*
Hemorrhages seriously
affected vision
5 eyes
1 eye
RPE tear
1eye$
* : fisher exact test
$ : did not affect vision

13. Discussion the prevalence of PCV PDT with verteporfin
high in presumed exudative AMD in Asian
PDT with verteporfin
superior results for treating PCV compared with CNV secondary to AMD
In the era of anti-VEGF therapy
intravitreal bevacizumab
positive anatomic results such as resolution of fluid
certain amount of bevacizumab may act directly on the abnormal vasculature in the subretinal pigment epithelial spaces.
limited efficacy of bevacizumab monotherapy when treating the abnormal vasculature of PCV,
2 possible reasons
Insufficient amount of bevacizumab may reach the subretinal pigment epithelial spaces because of its larger molecular size
VEGF-independent nature of PCV

14. Discussion Current study
an additional positive effect of an intravitreal bevacizumab was observed in the visual outcomes through 1 year.
During the early treatment period, the efficacy of bevacizumab for improving BCVA was apparent.
maximum improvement in the BCVA at 3 months, which was attributed primarily to rapid resolution of the exudative fluid and fibrin induced by bevacizumab, as we observed previously.
The leakage from abnormal vessels was treated effectively through the reduction of VEGF.
Moreover, bevacizumab may prevent transient induction of VEGF after PDT and subsequent reaction of vessels.

15. Discussion
a significantly lower rate of subretinal or subpigment epithelial hemorrhages, or both, associated with PDT in the combined treatment group.
17.7% vs 4.9%
The development of subretinal hemorrhages after PDT
a characteristic adverse event after PDT used to treat PCV
physicians want to avoid.
suppression of hemorrhages
decreased vascular permeability
suppression of hemorrhages.
 encourage ophthalmologists to choose the combined therapy.

16. Discussion For the long-term VA
the impact of the combined therapy - decreased
lesion recurrences and atrophic tissue changes related to persistent lesions
Resolution of the original PCV vasculature
a similar rate between the treatments
the recurrence rates also were similar
Bevacizumab monotherapy
did not cause regression of the abnormal PCV vasculature
lesions may be attributed mainly to PDT alone
Factors associated with a better 12-month VA
combined therapy
better baseline VA
smaller lesion size
absence of PED

17. Discussion longer follow-up periods
additional sessions of PDT - for the recurrences
 increase of risks induced by PDT
(subretinal hemorrhages or ischemic damage of normal choroidal tissue)
PDT combined with an anti-VEGF drug can reduce those side effects of PDT
injection of an anti-VEGF drug without PDT is an option
 the appropriate combination of an anti-VEGF drug and PDT is important to maintain better VA for the long term.

18. Discussion PEARL Trial  ranibizumab monotherapy
6-month interim results of monthly injections of ranibizumab
The results showed that ranibizumab monotherapy improved the mean VA at 6months by a mean of 7.2 letters and that 2 patients (17%) gained more than 15 letters.
That seemed almost the same as the visual results in our combined therapy group at 12 months.
the polypoidal lesions seen on ICGA decreased in 4 eyes (33%) at 6 months
the smaller molecular size of ranibizumab compared with bevacizumab
monthly continuous injections may enable the drug to penetrate into the subretinal pigment epithelial space more efficiently
However, difficulties in achieving complete resolution
 ranibizumab monotherapy
- potential for continuous risk of recurrences.

19. Discussion The current study was limited EVEREST Study
Retrospective and not a randomized, comparative trial.
However,
the absence of bias in the choice of the initial treatment
a relatively large number of eyes that had not received any previous treatments
EVEREST Study
prospective randomized clinical trial
6-month results
PDT combined with intravitreal ranibizumab
PDT monotherapy
Ranibizumab
helpful to know which treatment should be chosen as the initial therapy
although the differences of efficacy between ranibizumab and bevacizumab remained to be clarified.