Optical Coherence Tomography Angiography and Fibrotic Choroidal Neovascularization in Age-Related Macular Degeneration

Eric Souied and Alexandra Miere

5.1 Introduction

Choroidal neovascularization (CNV) is a key component in the pathogenic sequence of neovascular age-related macular degeneration (AMD), leading to loss of central vision over time.¹ While we know today that AMD pathogenesis incorporates a series of factors such as patient age, metabolic dysfunction, oxidative stress, and circulatory disturbances,² recent studies have emphasized on the decisive role played by the inflammatory immune response in both the formation and the progression of CNV.³ Along with geographic atrophy (GA), subretinal fibrosis is a key feature of end-stage AMD.⁴ With the advent of anti–vascular endothelial growth factor (anti-VEGF) treatment for neovascular AMD, vision improvement has been possible in 30 to 40% of the patients.^5,​6 However, due to the complex interaction between cytokines, such as VEGF, inflammatory cells, and extracellular matrix in the formation of CNV, the response to anti-VEGF therapy is somewhat limited⁷ and the natural history of neovascular AMD ultimately leads to either subretinal fibrosis or macular atrophy, with subsequent poor functional prognosis.

5.2 Subretinal Fibrosis

Subretinal fibrosis is the consequence of complex tissue repair mechanisms and may present either during the natural healing process⁷ or during anti-VEGF treatment.⁵ Until recently, the imaging of subretinal fibrosis has been based mainly on the combined use of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT), which allowed correlation analysis between the angiographic lesion and the corresponding SD-OCT anomaly. On FA, fibrotic CNV is characterized by hyperfluorescent lesions with no leakage in the late frames of the examination, while SD-OCT reveals a compact, subretinal, hyper-reflective lesion, of variable thickness, with possible loss of adjacent retinal pigment epithelium (RPE) and ellipsoid zone.^8,​9 Although multimodal structural imaging offers indirect signs of neovessel activity (leakage on FA, subretinal/intraretinal fluid and pigment epithelium detachment on SD-OCT), it does not have the ability to discriminate the various components of a fibrotic scar. The functional outcome of a patient with neovascular AMD could accurately be predicted by differentiating between active neovascular tissue and inactive fibrous tissue.

Optical coherence tomography angiography (OCTA), within the RTVue XR Avanti, with AngioVue software (Optovue, Inc., Freemont, CA) is a new imaging technique that uses the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm to generate amplitude-decorrelation angiography images. Visualization of blood flow allows a detailed evaluation of the retinal microcirculation and neovascular lesions.^10,​11

In a previous paper,¹² we described the OCTA features of subretinal fibrosis secondary to neovascular AMD and compared the findings with those of conventional imaging. The eyes included in the study were classified into two groups, based on FA and SD-OCT findings. In group A were included eyes with evidence of subretinal fibrosis that showed no exudative (subretinal or intraretinal fluid) on SD-OCT over the last 6 months. In group B were included eyes presenting with subretinal fibrosis and recent (<6 months) exudative signs: subretinal and/or intraretinal fluid, as detected on SD-OCT.

OCTA was able to reveal almost constantly (46 of 49 eyes; 93.8%) a perfused vascular network within the fibrotic scar, with subsequent architectural changes at the outer retina and choriocapillaris levels. In our analysis, three major neovascular patterns, described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%) have emerged. Furthermore, two types of hyporeflective structures, for which we coined the terms large flow void and dark halo, were observed in 63 and 65% of eyes, respectively.¹² Pruned vascular tree ( ▶ Fig. 5.1a) consisted of a neovascular network formed by dilated vessels with irregular flow and without any thin capillaries visible when segmenting the fibrotic scar in the OCTA. The pruned vascular tree pattern was present in 50% of study eyes, independently or combined with another pattern. A central feeder vessel was detected in the choriocapillaris segmentation in all cases of pruned vascular tree. Tangled network ( ▶ Fig. 5.1b), on the other hand, was characterized on OCTA images by high-flow, interlacing vessels, visible in the segmentation corresponding to the fibrous scar. The third pattern was called the vascular loop ( ▶ Fig. 5.1c), represented by a convoluted network on OCTA images corresponding to the fibrotic lesion. The presence of two types of dark lesions, flow void and dark halo, could be distinguished in more than half of the study eyes ( ▶ Fig. 5.2). While the dark halo harbored the aspect of a dark ring in the choriocapillaris segmentation, surrounding the neovascular network( ▶ Fig. 5.2a), the large flow void presented as a diffuse lack of signal in the segmentation corresponding to the fibrotic scar, due to masking ( ▶ Fig. 5.2b).

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