geographic atrophy that does not extend to the center of the macula. Advanced or late AMD can be either non-neovascular (dry, atrophic, or nonexudative) or neovascular (wet or exudative). Advanced non-neovascular AMD is characterized by drusen and geographic atrophy extending to the center of the macula while advanced neovascular AMD is characterized by CNV and subsequent scar [21, 22].

Retinal Angiomatous Proliferation

Retinal angiomatous proliferation (RAP) is largely considered a subset of AMD with a different disease course, pathology, and response to treatment compared with typical neovascular

AMD. In AMD, CNV originates below the RPE, in the choroidal circulation, and progresses into the retina. In advance neovascular AMD, there is then a communication between the choroidal circulation and the retinal circulation [23, 24]. RAP lesions are presumed to originate in the retinal circulation (as opposed to choroidal circulation) and ultimately form a retinal choroidal anastomosis in the late stages. RAP lesions may represent up to 15% of newly diagnosed wet AMD patients. Epidemiologic characteristics of patients with RAP include older age (81–82 years), Caucasian, female, and bilateral predilection. RAP lesions tend to be more aggressive with a worse clinical course than typical neovascular AMD and may be less responsive to anti-VEGF therapy (Fig. 3.8) [25–27].

A three-stage classification has been proposed to describe the progression of RAP lesions. Stage 1, intraretinal neovascularization (IRN) is usually slow-growing and asymptomatic. The location is usually extrafoveal and has not been described in the peripapillary area. IRN can result in intraretinal edema and multiple retinal hemorrhages. Fluorescein angiography usually reveals a focal area of intraretinal staining with indistinct borders corresponding to the IRN. This can be confused with idiopathic juxtafoveal telengectasia and classic AMD CNV lesions.

Pearl

Consider a diagnosis of RAP in cases with focal intraretinal hemorrhages, cystic macular edema, and a poor response to antiVEGF therapy.

Stage II, subretinal neovascularization (SRN), is seen when the vessels proceed posteriorly beyond the photoreceptor level and into the subretinal space. At this stage, detachment of the neurosensory retina can ensue with further intraretinal edema. SRN may reach the RPE causing a PED.

Stage III, choroidal neovascularization (CNV), is diagnosed when vascularized PED are seen. At this stage, the neovascularization is being fed by the choroidal circulation.

ICG angiography is superior to FA in diagnosing RAP cases. A focal “hot spot” of intense hyperfluorescence corresponding to the area of activity can be seen in all stages. ICG angiography better images the presence of vascularized PED, because the serous component of PED remains dark during the study, as opposed to hyperfluorescence on FA, and the vascular component appears as hyperfluorescence [25].