**3.1 Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)/acute multifocal ischemic choriocapillaritis (AMIC)**

APMPPE is an idiopathic, commonly bilateral although asymmetric, disorder affecting young healthy adults who complain of having visual loss, photopsias, and paracentral scotomas of acute onset. However, there have been some unilateral cases or delayed involvement of the second eye by several weeks [20].

The disease origin was first attributed to the RPE by Gass in 1968 [21]; hence the name, however, Deutman and coworkers [22], in the same period, hypothesized that it is a disease primarily affecting the choriocapillaris; therefore, they suggested the name acute multifocal ischemic choroidopathy (AMIC). This last term seems to be more proper as multimodal imaging has demonstrated [9].

Fundus photography shows multifocal, yellowish creamy, or pale discolored placoid chorioretinal lesions [23], located posterior to the equator (generally at the posterior pole) (**Figure 2**) that tend to progressively fade over the weeks, although new lesions may appear more peripherally later without extending beyond the equator, resulting in hyperpigmentation (clumping of pigment) and chorioretinal atrophy with potential damage to visual function.

FFA shows hypofluorescent lesions in early phases due to choriocapillaris nonperfusion, becoming hyperfluorescent by exudation and pooling in late frames due to increased permeability of retinal vascular plexuses induced by the massive ischemia in choriocapillaris and therefore in the overlying outer retina (**Figure 2**), which correspond to the yellow discolored plaques seen on fundus examination [3]. Inactive lesions appear hyperfluorescent due to window defects derived from RPE atrophy and blocked fluorescence from pigment clumping [24].

ICGA exhibits geographic hypofluorescent spots across all phases due to choriocapillaris non-perfusion. Acute lesions are more numerous or extensive than those seen clinically or on FFA [23] suggesting a primary choroid involvement. Inactive lesions tend to become smaller, probably due to the absence of swollen outer retina and RPE secondary to choroidal ischemia, and thus, less blockage [24]. When healed, hypofluorescence can also completely resolve except for a few areas of persistent hypofluorescence due to chorioretinal atrophy.

FAF shows hypoautofluorescence in acute lesions due to the blocking effect of overlying retinal edema [25] and hyperautofluorescence in areas where loss of photoreceptor outer segments has occurred causing increased exposure of RPE lipofuscin (**Figure 2**). Healed lesions develop increased central hyperpigmentation appearing hyperautofluorescent and a surrounding depigmentation zone that shows hypoautofluorescence due to RPE dysfunction/damage/atrophy in areas with severe vascular drop out that do not always correlate with the fundus lesions and/or FFA, and are fewer in number, implicating a primary choroidal alteration. These patterns in advanced lesions suggest centripetal contraction of the placoid lesions with atrophy and depigmentation of surrounding RPE cells [13].

## **Figure 2.**

*Patient presents a yellowish confluent placoid chorioretinal lesion. (a) On optical coherence tomography (OCT), there is loss of outer retina and EZ with a hyperreflectivity lesion nasal to the fovea. Optical coherence tomography angiography (OCT-A) demonstrates flow deficit at the level of choriocapillaris. (b) Later, FFA was made showing early hypofluorescence and late hyperfluorescence. (c) FAF shows mixed areas with hypo/ hyperautofluorescence at the initial visit and hypoautofluorescence in follow-up. (d) EZ: Ellipsoid zone.*
