Interval of Disease Inactivity After Complete Polypoidal Regression in PCV Receiving Aflibercept

Description

Primary objective:

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

Secondary objectives:

1. To determine the rate of polypoidal regression compared with baseline at 3, 6, 12, and 24 months following intravitreous aflibercept "treat and extend" regimen
2. 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.
3. To determine the correlation of changes at week 12 with changes at 12 months and 24 months
4. 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

Study design:

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

Methods

• 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

  follows

• 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.

  Definitions

• 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.

Details