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Arch Ophthalmol. 2004;122:1546-1547.

Ocular photodynamic therapy (PDT) with verteporfin has been shown to be an effective treatment for occult subfoveal choroidal new vessels (CNV) in age-related macular degeneration, but is associated with acute severe vision decrease (ASVD) in 4.4% in patients who received the treatment.¹

In this case the patient complained of decreased vision within hours of treatment, affording the opportunity to examine and assess the mechanism of vision loss 4 hours after therapy.

Report of a Case
An 82-year-old female patient had a sudden decrease in visual acuity. On examination, her acuity had decreased from 20/30 to 20/40 OU and her fundus showed a mild mottling of the pigment epithelium and no evidence of hemorrhage or exudative abnormalities. Fluorescein angiography showed an occult subfoveal CNV of 2.5 disc areas in size (Figure 1). On the basis of recent disease progression² and small lesion size she was treated with PDT. Following infusion of verteporfin (6 mg/m²), laser light at 698 nm was applied using a 3.5-mm spot, with an intensity of 600 mW/cm²for 83 seconds.

View larger version (119K): [in this window] [in a new window] Figure 1. A midphase fluorescein angiogram of the left eye showing stippled hyperfluorescence in the central macular area and no obvious serous retinal detachment.

Two to 3 hours later, the patient reported a dramatic decrease in her central vision with increased distortion and was examined 4 hours after PDT. Her Snellen visual acuity was 20/200 OU. Stereoscopic fluorescein and indocyanine green angiography revealed a gross central serous retinal detachment and outlined the CNV within the choroid (Figure 2). There was an intense spot of hyperfluorescence on the superotemporal margin of the CNV indicating a focal area of hyperpermeability. This was confirmed in the midphase showing a pool of indocyanine green collecting under the pigment epithelium (Figure 3). Over the next few days, the patient reported gradual disappearance of the "gray shadow" obscuring her vision and a return of her ability to read. After 4 days, the visual acuity returned to 20/40 OU and angiography confirmed complete closure of the occult CNV, cessation of hyperpermeability and leakage, and resolution of the retinal detachment in parallel with a return to pretreatment visual acuity. The visual acuity improved and remained stable at 20/30 OU on examination at 3, 6, and 9 months without further treatment.

View larger version (92K): [in this window] [in a new window] Figure 2. A and B, Stereopair of an early-phase indocyanine green angiogram 4 hours after photodynamic therapy, showing a markedly elevated serous detachment and a new vessel lesion above the level of the choroidal vessels with an acute leak at its superotemporal margin. C and D, Stereopair of an early-phase indocyanine green angiogram 4 days after photodynamic therapy. The serous detachment has significantly resolved and the neovascular lesion is nonperfused.

View larger version (105K): [in this window] [in a new window] Figure 3. A and B, Midphase (35 seconds) fluorescein angiograms showing the marked leakage of fluorescein at 4 hours and cessation of leakage at 4 days after photodynamic therapy. C and D, Midphase (9 minutes) indocyanine green angiograms showing the marked leakage of dye at 4 hours and cessation of leakage at 4 days after photodynamic therapy.

Comment
The 4-hour findings in our case were consistent with the preclinical studies which showed that shortly after PDT, the O₂-radical–mediated damage to the cytoskeleton causes rounding and contraction of the endothelial cells,³ interruption of the interendothelial cell tight junctions, and exposure of the subendothelial basement membrane. Histamine is released from the damaged endothelium, and activated polymorphonuclear leukocytes aggregate to the vessel wall, leading to an increase in vascular permeability and a propensity for exudation and edema.⁴ The 4-day findings were consistent with the studies showing that PDT damages membrane lipids, thus triggering the release of von Willebrand factor, thromboxane, and other clotting factors, and leads to platelet activation.^5-6 The platelets adhere to the collagen of the exposed subendothelial basement membrane and eventually thrombose the vessel.

Our findings also mimic those seen on ocular coherence tomography, which defined an initial acute inflammatory response with increased subretinal fluid, and a subsequent resolution of subretinal fluid with choroidal hypoperfusion.⁷

This patient suffered ASVD as defined by the Photodynamic Therapy Study Investigation, defined as the loss of at least 20 letters of visual acuity within 7 days of therapy.¹ It was observed in 4.4% (10 patients) and 0.75% (3 patients) of patients treated with verteporfin for age-related macular degeneration in the Verteporfin in Photodynamic Therapy Trial and the Photodynamic Therapy Study Investigation, respectively.^{1, 8} No such cases were identified within the placebo-treated groups.¹ The cases of ASVD in these trials were identified by a routine telephone call to patients 2 to 4 days after treatment. Symptomatic patients were asked to return promptly for reexamination. Most of these cases occurred after their first treatment. Many occurred on the same day or the day after treatment, although the exact time of vision loss was not reported. Our patient became symptomatic within hours of treatment and was reexamined almost at 4 hours after PDT, affording the opportunity to document and analyze the mechanism of her vision loss.

Some identifiable causes of ASVD following PDT from the clinical trials were extensive subretinal exudation, subretinal pigment epithelial hemorrhage, and suprachoroidal hemorrhage with retinal detachment and vitreous hemorrhage⁸. In approximately half the cases, no obvious cause was found.¹ It is possible that subretinal exudation was the underlying cause of the ASVD in these cases, but it had resolved by the time of examination.

This report shows that ASVD due to exudation and subsequent serous retinal detachment may occur within hours of PDT before the new vessel is thrombosed. Closure of the vessel was associated with complete resolution and an excellent long-term result.

The authors have no relevant financial interest in this article.

AUTHOR INFORMATION

Paul Beaumont, FRANZCO; Charmaine S. Lim; Andrew Chang, FRANZCO; Kwon Kang, MBBS

Correspondence: Dr Beaumont, 13th Floor, 187 Macquarie St, Sydney NSW 2000, Australia (pbeau{at}ozemail.com.au).

REFERENCES
1. Verteporfin In Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization–verteporfin in photodynamic therapy report 2. Am J Ophthalmol. 2001;131:541-560. FULL TEXT | ISI | PUBMED 2. Verteporfin Roundtable 2000 and 2001 Participants; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group Principal Investigators; Verteporin in Photodynamic Therapy (VIP) Study Group Principal Investigators. Guidelines for using verteporfin (Visudyne) in photodynamic therapy to treat choroidal neovascularisation due to age-related macular degeneration and other causes. Retina. 2002;22:6-18. FULL TEXT | ISI | PUBMED 3. Fingar VH. Vascular effects of photodynamic therapy. J Clin Laser Med Surg. 1996;14:323-328. PUBMED 4. Fingar VH, Wieman TJ, Haydon PS. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992;52:4914-4921. FREE FULL TEXT 5. Ben-Hur E, Heldman E, Crane SW, Rosenthal I. Release of clotting factors from photosensitized endothelial cells: a possible trigger for blood vessel occlusion by photodynamic therapy. FEBS Lett. 1988;236:105-108. FULL TEXT | ISI | PUBMED 6. Foster TH, Primavera MC, Marder VF, Hilf R, Sporn LA. Photosynthesized release of von Willebrand factor from cultured human endothelial cells. Cancer Res. 1991;51:3261-3266. FREE FULL TEXT 7. Rodgers AH, Martidis A, Greenberg PB, Puliafito CA. Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization. Am J Ophthalmol. 2002;134(4):566-576. FULL TEXT | ISI | PUBMED 8. 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;117:1329-1345. FREE FULL TEXT

SECTION EDITOR: W. RICHARD GREEN, MD

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