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Clinicopathologic Reports, Case Reports, and Small Case Series
November 2002

Apparent Disappearance of Choroidal Neovascularization After Initial Photodynamic Therapy With Verteporfin

Arch Ophthalmol. 2002;120(11):1588-1590. doi:

Photodynamic therapy with verteporfin (Visudyne; Novartis AG, Switzerland), also termed verteporfin therapy, can reduce the risk of moderate and severe vision loss in selected patients with choroidal neovascularization (CNV).14 The Japanese Age-Related Macular Degeneration Trial (JAT), a photodynamic therapy trial started in May 2000, was designed to evaluate the safety and fluorescein angiographic effects of verteporfin therapy. This report describes an unusual case from this trial in which subfoveal CNV was no longer apparent on fluorescein angiography after an initial application of photodynamic therapy with verteporfin. There was no obvious fluorescence from fibrosis or atrophy of the retinal pigment epithelium within the area initially occupied by CNV.

Report of a Case

A 79-year-old Japanese woman, who had visual disturbance in her left eye for 2 years before seeking treatment, subsequently developed decreased vision in her right eye. She was referred to Osaka University Hospital, Osaka, Japan, in August 2000. Her best-corrected visual acuity (approximate Snellen equivalent) was 20/126 OD and 20/200 OS. Ophthalmoscopic examination showed a subfoveal lesion with subretinal hemorrhage in the right eye (Figure 1, A) and atrophy in the macular area of the left eye. Fluorescein angiography showed leakage from CNV in a pattern composed of at least 50% classic CNV (a predominantly classic lesion1) with a greatest linear dimension of 3400 µm (Figure 1, B). After reviewing the risks and benefits of participating in the JAT, the patient signed a consent form previously approved by the local institutional review board and enrolled in the JAT in October 2000. Verteporfin therapy was performed without any complications, following the protocol used in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation.

A, A color fundus photograph shows subretinal hemorrhage surrounding
a subfoveal lesion. B, A late-phase frame fluorescein angiogram shows leakage
from choroidal neovascularization (CNV) under the center macula with additional
slight hyperfluorescence without leakage just superior to the lesion. C, A
color fundus photograph taken 3 months after photodynamic therapy with verteporfin
shows resolution of the hemorrhage and no fibrosis or significant retinal
pigment epithelial abnormalities within the region previously occupied by
CNV. D, A late-phase frame fluorescein angiogram shows no leakage or staining
within the area previously occupied by CNV. Fluorescent staining, without
leakage, is unchanged just superior to the central macula. E, A color fundus
photograph taken 6 months after photodynamic therapy with verteporfin shows
no fibrosis and only slightly increased pigmentation within the region previously
occupied by CNV. F, A late-phase frame fluorescein angiogram shows no leakage
or staining within the area previously occupied by CNV.

A, A color fundus photograph shows subretinal hemorrhage surrounding a subfoveal lesion. B, A late-phase frame fluorescein angiogram shows leakage from choroidal neovascularization (CNV) under the center macula with additional slight hyperfluorescence without leakage just superior to the lesion. C, A color fundus photograph taken 3 months after photodynamic therapy with verteporfin shows resolution of the hemorrhage and no fibrosis or significant retinal pigment epithelial abnormalities within the region previously occupied by CNV. D, A late-phase frame fluorescein angiogram shows no leakage or staining within the area previously occupied by CNV. Fluorescent staining, without leakage, is unchanged just superior to the central macula. E, A color fundus photograph taken 6 months after photodynamic therapy with verteporfin shows no fibrosis and only slightly increased pigmentation within the region previously occupied by CNV. F, A late-phase frame fluorescein angiogram shows no leakage or staining within the area previously occupied by CNV.

One week after treatment, the patient's best-corrected visual acuity (approximate Snellen equivalent) was 20/160 OD. Ophthalmoscopic examination of her right eye showed no change to the subretinal hemorrhage. Fluorescein angiography showed no leakage from CNV and no fluorescein staining in the macular area previously occupied by CNV.

At 3 and 6 months after treatment, best-corrected visual acuity (approximate Snellen equivalent) improved to 20/100 OD and 20/80 OD, respectively. No CNV was detected in her right eye on ophthalmoscopic examination at either of these visits. Fluorescein angiography at the 3-month (Figure 1, C and D) and 6-month (Figure 1, E and F) examinations showed no abnormal fluorescence within the region originally occupied by CNV, although some fluorescence superior to the macula was noted.

Comment

This case from the JAT demonstrates an apparent disappearance of CNV for at least 6 months on fluorescein angiography following a single application of photodynamic therapy with verteporfin. There was no fluorescein staining of fibrosis or atrophy of the retinal pigment epithelium within the area originally occupied by CNV. The new area of fluorescence noted superior to the treated area cannot be explained at this time. This outcome has not been seen by any of us before, including one of us (N.M.B.) who served as an investigator at the Photograph Reading Center, Johns Hopkins University, Baltimore, Md, and who reviewed 1-week, 4-week, and 12-week posttreatment fluorescein angiograms from phase 1 and 2 studies and angiograms from phase 3 trials14 evaluating verteporfin therapy.5,6 Although complete absence of fluorescein leakage from CNV 1 week after photodynamic therapy has been reported,5 leakage usually reappears within 12 weeks in approximately 90% of treated cases,1 with fluorescein staining of fibrovascular tissue in the remaining cases (N.M.B., unpublished observations, 2001). The absence of fluorescence following verteporfin therapy may be due to isofluorescence within the area of treatment, wherein the pigmentation in the macular area was sufficient to obscure any fluorescence that might otherwise cause staining of the choroidal neovascular lesion. As this is the first verteporfin therapy trial exclusively in a Japanese population, the fluorescein findings may be related specifically to this population, although such findings have not been reported in any of the few Asian participants in a previous verteporfin therapy trial.3 Longer-term follow-up continues.

This study was supported by Novartis Ophthalmics, Bülach, Switzerland, and QLT Inc, Vancouver, British Columbia. Dr Bressler has been paid as a consultant by QLT Inc and Novartis Ophthalmics. The terms of this agreement are being managed by Johns Hopkins University in accordance with its conflict of interest policies.

Corresponding author and reprints: Miki Sawa, MD, Department of Ophthalmology, Osaka University Medical School, Room E7, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan (e-mail: sawamiki@ophthal.med.osaka-u.ac.jp).

References
1.
Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Study Group, Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials: TAP report 1. Arch Ophthalmol. 1999;1171329- 1345Article
2.
Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Study Group, Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials: TAP report 2. Arch Ophthalmol. 2001;119198- 207
3.
Verteporfin in Photodynamic Therapy Study Group, Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin: one-year results of a randomized clinical trial: VIP report 1. Ophthalmology. 2001;108841- 852Article
4.
Verteporfin in Photodynamic Therapy Study Group, Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization: VIP report 2. Am J Ophthalmol. 2001;131541- 560Article
5.
Miller  JWSchmidt-Erfurth  USickenberg  M  et al.  Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study. Arch Ophthalmol. 1999;1171161- 1173Article
6.
Schmidt-Erfurth  UMiller  JWSickenberg  M  et al.  Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Arch Ophthalmol. 1999;1171177- 1187Article
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