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Imaging of Exudative Age-Related Macular Degeneration: Toward a Shift in the Diagnostic Paradigm?

Exudative age-related macular degeneration (AMD) remains a severe disease despite the widespread use of intravitreal anti–vascular endothelial growth factor (VEGF) agents. Despite adequate therapy, patients may still develop vision loss, evolution toward fibrosis, or massive subretinal bleeding, and frequently develop geographic atrophy that will usually affect central vision after a few years.1–3 Early diagnosis of choroidal neovascularization (CNV) is of great importance to maintain a significant level of visual acuity. For decades and up to the first anti-VEGF trials,4 fluorescein angiography (FA) was the gold standard for the diagnosis of CNV both in clinical trials and in clinical practice. Fluorescein angiography is a dye-based imaging tool in which CNV can be diagnosed as an early or late hyperfluorescent lesion, well defined or ill defined, with late leakage. Fluorescein angiography also allowed one to differentiate classic from occult CNV, a very important distinction in the laser photocoagulation era.5 Indocyanine-green angiography (ICGA) was suggested as an important adjunctive dye-based imaging tool, especially in determining the size and localization of occult CNV and allowed recognition of chorioretinal anastomoses, also termed retinal angiomatous proliferation, and polypoidal choroidal vasculopathy.6–9 However, despite its usefulness, ICGA has not joined or replaced FA as the gold standard for diagnosis. Diffusion of use of ICGA remained limited even among retina specialists, and subsequently its use decreased progressively.10,11 Both FA and ICGA are invasive tools, with possible severe systemic side effects of intravenous injection of these dyes.12 Optical coherence tomography (OCT) revolutionized imaging of the posterior pole, as a painless, noncontact, noninvasive method of imaging and analyzing the different layers of the posterior pole.13,14 As it was pointed out in a recent review,15 development of OCT paralleled the advent of anti-VEGF as first-line therapy of exudative AMD. Optical coherence tomography allowed tailoring of the treatment in flexible regimen, such as pro re nata or “treat-andextend” strategies.16,17 Furthermore, rapid improvement of OCT technology, particularly the availability of spectral-domain OCT (SD-OCT), allowed a nearhistologic resolution to resolve the different retinal layers. Initially, studies tried to compare the relative sensitivity and specificity of time-domain or SD-OCT versus FA,18 but combined FA and OCT came to be considered the new gold standard for diagnosis of exudative AMD.15 This combined imaging also allowed for reclassification of the different subtypes of CNV as Type 1 or subepithelial neovascularization, Type 2 or preepithelial neovascularization, and Type 3 or retinal angiomatous proliferation lesion.19 This new classification of neovascular AMD based on combined FA and OCT has been demonstrated to be superior to FA alone in determining the incidence of the various CNV subtypes,20 their different visual prognoses21,22 and the incidence of geographic atrophy associated with these different subtypes.23 Combining FA and OCT has been demonstrated to be more clinically meaningful in our clinical practice than using FA alone in determining the CNV subtypes, their prognosis, defining a therapeutic strategy, and choosing a dosing regimen. However, new developments in OCT technology may change our diagnostic paradigm. Optical coherence tomography-angiography (OCTA) is a new, noninvasive imaging, using en-face imaging and different algorithms, which allows a fast and noninvasive in vivo analysis of the morphology of both the superficial and deep capillary plexuses, as well as the outer retina and the choriocapillaris. Since the first imaging of CNV because of AMD with OCTA,24 this technique has been demonstrated in numerous studies to have excellent sensitivity and specificity to diagnose and monitor neovascular activity in AMD.25–41 Because OCTA is always performed in association with structural OCT, a single noninvasive imaging tool allows imaging of None of the authors has any financial/conflicting interests to disclose. S. Y. Cohen is consultant for Alcon, Allergan, Bayer, Novaryis, and Thea. S. Mrejen is consultant for Bayer and Novartis.