High-speed indocyanine green angiography shows potential for management when anti-vascular endothelial growth factor treatment fails

April 15, 2008

Arteriolarization, with a large artery feeding many branching arterioles, may explain why some eyes with choroidal neovascularization fail to respond to anti-vascular endothelial growth factor treatment. Dynamic high-speed indocyanine green angiography can identify this morphology and be used to direct photodynamic therapy toward the feeder artery. Initial results with this intervention are promising.

Key Points

Indian Wells, CA-Experience with indocyanine green angiography (ICGA)-directed verteporfin (Visudyne, Novartis) photodynamic therapy (PDT) targeting feeder vessels indicates that it may provide effective treatment for choroidal neovascularization (CNV) that is resistant to anti-vascular endothelial growth factor (VEGF) therapy, said Scott W. Cousins, MD, at the annual meeting of the American Society of Retina Specialists.

The rationale for using ICGA-directed PDT is based on the concept that arteriolarization may be the basis for failure in many CNV lesions demonstrating anti-VEGF treatment resistance. Dr. Cousins presented evidence to support this hypothesis from a review of anti-VEGF-responsive and -resistant CNV lesions imaged with dynamic high-speed ICG angiography, and he reported results from a retrospective review demonstrating anatomic resolution of leakage and pigment epithelial detachment in 32 (94%) of 34 anti-VEGF-resistant eyes treated with ICGA-directed PDT.

"A retrospective review from our institution highlights that anatomic resistance to anti-VEGF therapy is not uncommon. Using optical coherence tomography [OCT] or fluorescein angiography, we found 25% of 99 eyes demonstrated either lack of anatomic resolution following anti-VEGF induction therapy or frank progression during ongoing treatment," said Dr. Cousins, the Robert Machemer, MD, Professor of Ophthalmology, Duke University, Durham, NC. "The relatively high prevalence of this problem raises the questions of what is the biology driving these lesions and what to do for eyes with anti-VEGF-resistant CNV."

The presence of arteriolarization is characterized using dynamic high-speed ICGA (Heidelberg Retinal Angiograph or Spectralis, Heidelberg Engineering) that is able to identify three distinct components of CNV lesions: feeding arteries and their branching arterioles, capillaries, and a draining venule.

'Spectrum of morphology'

"Review of high-speed ICG images from CNV lesions reveals a spectrum of morphology ranging from one that is capillary-dominated with tiny feeder vessels to others where there is a huge feeder artery with many branching arterioles," Dr. Cousins explained. "In reality, most cases fall somewhere in the middle."

He presented a series of images that demonstrated the presence of an arteriole-dominated lesion in eyes with "thick" classic CNV or occult CNV that also demonstrated anti-VEGF treatment resistance, however. Eyes responding to anti-VEGF therapy were characterized by capillary-dominated CNV.

Retrospective review

To determine the effectiveness of ICGA-directed PDT for anti-VEGF-resistant CNV in eyes with arteriolarized vascular complexes, Dr. Cousins and colleagues undertook a retrospective review of data from a non-controlled series of 34 eyes of 34 patients seen at two retina practices. The eyes were classified as demonstrating anti-VEGF therapy resistance based on either a lack of anatomic improvement according to OCT and fluorescein angiography findings after induction with ranibizumab (Lucentis, Genentech) or bevacizumab (Avastin, Genentech) or CNV progression during maintenance therapy.

Twenty-six eyes met the first criteria for resistance, and eight eyes demonstrated either lesion enlargement or new hemorrhage with ongoing injections. All eyes also had arteriolarized vascular complexes identified by dynamic ICG with an evident feeder vessel perfusing numerous smaller distal vessels and rapid filling times suggesting relatively high blood flow.

ICGA-directed PDT directed toward the feeder vessel was performed using a 1,000-µm spot size and either standard duration or half-duration PDT. In addition, intravitreal triamcinolone acetonide, 2 to 4 mg, was injected after PDT in all eyes, and 20 eyes received anti-VEGF therapy within 10 days of PDT.

Improvement

Of the 34 eyes treated, 32 demonstrated anatomic improvement by ICGA, fluorescein angiography, and OCT. The improvement was noted after the first feeder vessel-directed ICG in 28 eyes and after a second PDT session in four eyes.

Visual acuity for the group increased by a mean of 1.2 lines, with eight eyes demonstrating a gain of three or more lines and only one eye losing three lines.

Dr. Cousins noted that the durability of the effect appeared to persist for about 6 months.

"Twenty-eight eyes were stable for at least 6 months, but then many developed recurrent leakage between 6 and 9 months," he reported.

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