Polypoidal choroidal vasculopathy (PCV), a subtype of neovascular age-related macular
degeneration (NV AMD), is an important cause of central visual loss, especially among Asian
and African descendants. PCV is characterized by the presence of hyperfluorescent polypoidal
lesions, with or without branching vascular network, identified on indocyanine green
angiography (ICGA), currently the gold standard for PCV diagnosis.
In addition to visual improvement from baseline, polypoidal regression or complete
disappearance of polypoidal lesions on ICGA has been considered an important treatment
outcome in large PCV trials including the PLANET1 and EVEREST II2 studies. Rate of polypoidal
regression following intravitreous aflibercept monotherapy was 33% in the PLANET study1 year
2 and ranged between 55% to 78% in other Asian cohorts.3-4
Recently, our previous investigation5 on the timing of polypoidal regression following a
fixed-dosing aflibercept monotherapy (3 initial monthly injections, then q 8 weeks until 1
year) in 40 Thai PCV eyes suggested that, among 22 eyes (55%) with polypoidal regression at 1
year, a majority of them showed complete polypoidal regression before 6 months (median
duration of complete regression: 3 months (IQR, 2 months to 6 months).
However, due to the fixed-dosing regimen used in previous study, there are limited data on
how often polypoidal lesions remain regressed on ICGA when the treatment is deferred in eyes
with polypoidal regression, nor what changes might be seen subsequently on OCT when treatment
is deferred in this situation. Therefore, this study aims to determine the changes seen on
OCT subsequent to complete regression of polypoidal lesions on ICGA in PCV eyes following
intravitreous aflibercept treatment.
Results from this study may provide some insights on longer-term PCV management
To determine how long there is CNV inactivity on OCT (absence of intraretinal thickening,
intraretinal cystoid abnormalities, subretinal fluid, or enlarging pigment epithelial
detachments) in eyes with complete polypoidal regression on ICGA after receiving
intravitreous aflibercept injections over 2 years for PCV
- To determine the rate of polypoidal regression compared with baseline at 3, 6, 12, and
24 months following intravitreous aflibercept "treat and extend" regimen
- To determine the visual acuity change from baseline to 1 and 2 years following
intravitreous aflibercept "modified treat and extend" regimen and its correlation with
OCT or ICGA activity.
- To determine the correlation of changes at week 12 with changes at 12 months and 24
- To determine the incidence of newly developed or recurrent polypoidal lesions in eyes
with complete polypoidal regression after aflibercept treatment "treat and extend"
regimen over 2 years
Multi-center prospective case series. The overall study duration will be 3 years; 1 year for
recruitment and 2-year follow-up for each participant
- Overall study duration for each participant will be 24 months
- Eligible participants will receive 3 initial monthly intravitreous 2-mg aflibercept
injections (week 0, 4, 8), then management will be based on ICGA findings at week 12 as
- Complete polypoidal regression on ICGA: defer intravitreous aflibercept injection, and
follow-up monthly with OCT monitoring thereafter until 1 year, and bimonthly in year 2.
If subretinal or intraretinal fluid is seen on OCT during the follow-up period, an
interval of disease inactivity is determined. Such study eye with re-activation is
considered met primary end point and will receive intravitreous anti-VEGF treatment
according to "treat and extend" regimen as described below.
- Incomplete or worsening polypoidal regression on ICGA: continue additional 3
intravitreous aflibercept injection, and repeat ICGA at week 24
- At week 24, if there is a presence of complete polypoidal regression on ICGA, defer
intravitreous aflibercept injection, and follow-up monthly with OCT monitoring
thereafter until 1 year, and bimonthly in year 2. If subretinal or intraretinal
fluid is seen on OCT during the follow-up period, an interval of disease inactivity
(primary outcome) is determined. Such study eye with re-activation is considered
met primary end point and will receive intravitreous anti-VEGF treatment according
to "treat and extend" regimen as described below.
- At week 24, if there is partial or no regression of polypoidal lesion, continue
intravitreous aflibercept injection with "treat and extend" regimen, which the
follow-up interval can be extended by 4 weeks up to 16 weeks if no disease activity
identified on color fundus photography or OCT. If disease activity recurs, shorten
follow-up interval by 4 weeks, remain injections at that interval until fluid
resolved, and re-extend by 2 weeks. Treatment interval will not be less frequent
than every 4 weeks (according to an approved label of intravitreous aflibercept in
Thailand). During follow-up, if an investigator suspect the presence of complete
polypoidal regression based on OCT findings, ICGA can be performed at any visit. If
complete polypoidal regression is present, defer the treatment and follow-up
monthly with OCT monitoring in year 1, and bimonthly in year 2.
- Photodynamic therapy can be applied at 1 year, if persistent fluid on OCT is
identified despite continuous intravitreous aflibercept injections.
Investigations at each visit
- Visual acuity measurement, color fundus photography (CFP), and SD-OCT will be performed
at each visit
- Fundus fluorescein angiography (FA) and indocyanine green angiography (ICGA) will be
performed at week 0 (baseline), 3, 6, 12, and 24 months, and at any time point showing a
recurrence of disease activity in eye that previously shown complete polypoidal
regression on ICGA, or at any time point an investigator suspect the presence of
complete polypoidal regression based on OCT findings.
- Disease activity on color fundus photography is defined as a presence of new retinal or
subretinal or sub-RPE hemorrhage
- Disease activity on OCT is defined as a presence of intraretinal or subretinal fluid or
new pigment epithelial detachment
- Polypoidal regression is defined as complete absence of hyperfluorescent lesions in an
area that previously had a polypoidal lesion on ICGA at baseline
- Partial polypoidal regression is defined as decrease of hyperfluorescent polypoidal
lesions either in size or number or both in an area previously identified as a
polypoidal lesion on ICGA at baseline
- Persistent or worsening polypoidal regression is defined as a persistent or enlargement
in size and number of hyperfluorescent lesions in an area previously identified as a
polypoidal lesion on ICGA at baseline
- Newly developed polypoidal lesion is defined as a presence of a polypoidal lesion not
previously identified on ICGA at baseline
- Recurrent polypoidal lesion is defined as a polypoidal lesion in an area previously
identified as polypoidal regression on ICGA.