Of these proposed acronyms, RAP is most commonly used in clinical practice.

Clinically, these lesions are often accompanied by focal hyperpigmentation. Other findings that may be present include microaneurysms, retinal vascular telangiectasias, dot intraretinal hemorrhages, right-angle venules and arterioles, and PEDs. Although a direct communication between the abnormal retinal vascular complex and the choroid is usually present, in a minority of patients the neovascular lesion may originate within the retina as a primary angiomatous complex without evidence of choroidal involvement [50]. In spite of the potential variation that may exist in the underlying pathophysiology, lesions that involve retinal vascular proliferation are considered to be a distinct subgroup of neovascular AMD for which anti- VEGF-based therapies appear to be effective [57].

Fundus Imaging Characteristics of Therapies for Neovascular AMD

Thermal Laser

Thermal laser photocoagulation, generally reserved for the treatment of extrafoveal or juxtafoveal CNV lesions [72], is a relic of the pre-anti- VEGF era when treated eyes often experienced a decline in visual acuity [73]. Patients treated with thermal laser are typically seen two and four weeks later with repeat fluorescein angiography. Previous laser treatment is discernible by hypofluorescence in the center of the lesion during the early and mid phases of the angiogram. Lingering subretinal fluid and focal hyperfluorescent leakage at the margin of the treated lesion on the angiogram are indicative of persistent CNV. In contrast, late staining of the lesion, particularly in the center without involvement of the edge, is commonly observed and does not usually necessitate additional laser treatment.

Recurrence of neovascularization following thermal laser treatment, which is defined by the appearance of new vessels six or more weeks later, is rather common [73]. Fundus and angiographic findings are variable and may include visible signs of exudation such as blood and lipid,

new focal area of hyperfluorescence at the margin of a previously treated area, or stippled hyperfluorescence with or without pronounced thickening at the level of the RPE, which would suggest new growth of occult CNV. Recurrences after thermal laser often occur in fovea-centric fashion, thus other forms of treatment are indicated.

Photodynamic Therapy

The area of neovascularization one week following PDT generally appears dark on ICG angiography due to a profound reduction of perfusion in the entire photosensitized area and surrounding choroid as well [74]. Interestingly, this is usually not observed in patients who have a retinal vascular contribution to the CNV. After treatment, choroidal reperfusion occurs gradually over several weeks, beginning with the larger vascular stumps first,followedbysmallervessels[74].Identification of these larger stumps on ICG angiography provided a rationale for feeder vessel treatment using thermal laser, with the aim of preventing reperfusion of the abnormal vascular structure.

In the main clinical trials of PDT for neovascular AMD, patients received regular 3-month follow-up visits with fluorescein angiography. Leakage on angiography three months after treatment served as an indication for retreatment, however this was not referred to as a recurrence since this was observed in almost all cases in the phase one and two studies [75, 76]. Indeed, at three-month follow-up in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Trial (TAP), 90% of patients still demonstrated leakage from CNV and were retreated accordingly [77]. Since PDT with verteporfin selectively occludes vessels within CNV but does not actually generate thermal damage, this short-lived cessation of leakage is not unexpected. In general, a variable number of periodic retreatments are necessary to maintain cessation of leakage and achieve reduction of lesion size. Although PDT is no longer employed as monotherapy in clinical practice, its use in combination with anti-VEGF therapy remains under investigation in clinical trials. Combination therapy for neovascular AMD will be presented in a later chapter.