Elsevier

Ophthalmology

Volume 110, Issue 7, July 2003, Pages 1306-1314
Ophthalmology

Changes in confocal indocyanine green angiography through two years after photodynamic therapy with verteporfin

Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 2000.
https://doi.org/10.1016/S0161-6420(03)00452-4Get rights and content

Abstract

Purpose

To evaluate vascular changes documented by confocal indocyanine green angiography (ICGA) through 2 years after photodynamic therapy (PDT) with verteporfin of neovascular age-related macular degeneration (AMD).

Design

Single-center, 2-year, randomized, double-masked, interventional, placebo-controlled trial (subset from Treatment of AMD with PDT Study [TAP]).

Participants

Sixty patients with subfoveal choroidal neovascularization (CNV) resulting from AMD.

Intervention

Patients were randomized in a ratio of 2:1 to a standard regimen using verteporfin therapy at a drug dose of 6 mg/m2 body surface area and a light dose of 50 J/cm2 or a sham treatment with placebo infusion and light exposure. Retreatments, if persistent fluorescein leakage from CNV was documented, were scheduled at 3-month intervals for up to 2 years. Confocal ICGA with tomographic sections was performed at baseline and continuously at the month 3, 6, 12, and 24 examinations using a standardized protocol.

Main outcome measures

Analysis included the size of the neovascular net, the area of late hyperfluorescence, and choroidal hypofluorescence during early- and late-phase imaging.

Results

In the verteporfin-treated group, the mean size of the CNV and the mean area of late leakage consistent with active leakage or staining showed no further enlargement at month 12 and were reduced at month 24. In the placebo-treated group, new vessels grew threefold compared with baseline and exhibited persistent late hyperfluorescence resulting from leakage at 24 months. Associated choroidal hypofluorescence within the treated area was significantly increased in eyes treated with verteporfin PDT compared with the control group during the first year, persisted during all ICGA phases, and was irreversible during follow-up. Image analysis revealed choroidal hypoperfusion with choriocapillary dropout, which correlated with chorioretinal atrophy clinically. Progressive destruction of choroidal integrity by fibrosis in control eyes led to a similar extent of collateral hypofluorescence in both groups through the 24-month examination.

Conclusions

Indocyanine green angiography is an important adjunct in the identification of vascular effects associated with verteporfin PDT. Repeated treatments effectively arrested CNV growth and reduced leakage activity. The collateral impairment of choroidal perfusion appears to influence the visual outcome of the treatment.

Section snippets

Patients and methods

This study was designed as an ancillary trial to the TAP Investigation, a randomized, double-masked phase III clinical trial that was performed in 22 tertiary referral centers in the United States and Europe.1, 2 The ICGA analysis was carried out as a prospective, single-center ancillary study. The protocol for this ancillary study complied with the Declaration of Helsinki and with the recommendations of the governing institutions and received the approval of the TAP Study Advisory Group.

Results

A total of 60 patients participated in the TAP trial at the Luebeck study center. All consecutive TAP participants underwent standardized ICGA at each presentation according to protocol and were included in the analysis. Double masking was maintained during the treatment procedure, the ICGA examinations, and the entire data analysis. Retrospective unmasking identified a group of 40 eyes assigned to verteporfin treatment, and a control group of 20 eyes assigned to sham treatment. Follow-up was

Discussion

Photodynamic therapy is an intervention specifically addressing a selective manipulation of vascular structures and provides an excellent rationale for the treatment of ocular neovascular disease. In the treatment of CNV lesions, obvious vascular effects, including vascular obliteration and resolution of leakage, are seen clinically and by FA. Indocyanine green angiography is a diagnostic method with a high sensitivity for the imaging of subretinal vascular layers such as the neovascular

References (18)

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Manuscript no. 220347

The Massachusetts General Hospital, Harvard Medical School, is an owner of the patent covering the use of verteporfin to treat ocular neovascular disease. U. Schmidt-Erfurth is an inventor on the patent. Massachusetts General Hospital’s institutional patent policy and procedures include royalty-sharing provisions for inventors.

The authors have no proprietary interest in the Heidelberg Retina Angiograph.

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