**3.2 Serpiginous choroiditis (SC)**

SC is a bilateral, although asymmetric, progressive, and recurrent ocular disorder, representing the most severe form of primary choriocapillaritis, probably because the vaso-occlusive involvement occurs in the larger arterioles producing a more widespread choriocapillaris non-perfusion with secondary involvement of the outer retina and RPE, and leading to an extensive and irreversible chorioretinal scarring if not treated promptly, in contrast to MEWDS, which involves the more distal end-choriocapillary vessels, causing less ischemia and consequently less damage that frequently is reversible [4]. Patients report decreased vision, metamorphopsias, scotomas, and photopsias.

Fundus photography shows gray-white-yellow choroidal active lesions [28] which start from the peripapillary region and spread centrifugally in a serpiginous pattern, hence the name. Rarely, macular may present without peripapillary involvement. Over time, these lesions become pigmented chorioretinal scars and recurrences can occur at the border of these atrophic lesions, weeks to years after prior episodes of inflammation (**Figure 3**).

FFA reveals active lesions with early diffuse hypofluorescence probably by blockage of the underlying choroidal fluorescence by swollen outer retina and RPE cells and/or impaired perfusion of choriocapillaris [24, 29] with late hyperfluorescence at the borders [28] by leakage of surrounding intact choriocapillaris [29]. Gradually,

## **Figure 3.**

*This patient presents a peripapillary chorioretinal scar affecting also the macula. (a) On FAF, lesions appear hypoautofluorescent. (b) OCT shows outer retina/RPE loss and choroidal thinning in the atrophic areas. In the left eye, there is also a subretinal hyperreflective lesion suggestive of CNV which is better defined by optical coherence tomography angiography (OCT-A) in the outer retina and choriocapillaris and with flow signals in the B-scan. OCT-A also shows flow deficit in choriocapillaris in both eyes. (c) RPE: Retinal pigment epithelium; CNV: Choroidal neovascularization.*

there is profuse leakage of the dye from larger choroidal vessels which is observed as hyperfluorescence of the lesion [30]. Early hyperfluorescence with late leakage may represent CNV, usually at the edge of lesions. Older atrophic lesions appear early hypofluorescent by the choriocapillaris atrophy and in late phases hyperfluorescent by diffuse staining of the chorioretinal scar [29]. Some areas show hypofluorescence by blockage (masking effect) from pigment clumping [3].

On ICGA, lesions appear hypofluorescent throughout all phases and are more extensive than FFA or clinically, as it represents both atrophic and active choriocapillaris non-perfusion which explains the pathophysiology. In addition, there may be a diffuse perilesional hyperfluorescent halo that indicates progression of disease [3].

OCT-A demonstrates areas of flow deficit at the level of the choriocapillaris which correlate the hypofluorescence on ICGA, what confirms the choriocapillaris nonperfusion as a primary alteration. Also, it is helpful in detecting CNV and monitoring treatment (**Figure 3**).

OCT shows outer retinal/RPE loss and choroidal thinning in the center of atrophic lesions (**Figure 3**), and at the border there is hyperreflectivity and thickening of the outer retina corresponding with ICGA halo around atrophic lesion and disruption of the EZ representing active lesions.

On FAF, active lesions appear with central hypoautofluorescence, when choriocapillaris and RPE are lost, surrounded by a hyperautofluorescent halo as choriocapillaris and RPE are still present but there is loss of photoreceptor outer segments (**Figure 3**).

## **3.3 Relentless placoid chorioretinitis (RPC)/ampiginous choroiditis (AC)**

Ampiginous choroiditis is an uncommon variant that overlap features of both APMPPE/AMIC and SC [9]. It is characterized by chronic and recurrent clinical course as SC unlike APMPPE/AMIC. Fundus photography shows an atypical distribution of lesions in the mid-periphery and posterior pole in contrast to APMPPE/ AMIC or SC which are usually limited to the posterior pole (**Figure 4**) and are smaller than SC and APMPPE/AMIC, approximately 1/2 disk area and more numerous than APMPPE/AMIC (50 or more). There is often active disease in both eyes simultaneously with white placoid lesions present throughout the fundus [31] in contrast to serpiginous chorioretinitis in which usually only one eye is active at a time [24].

Angiographic changes are comparable to SC [9, 23], but active lesions may start distant from previous lesions, but in SC they usually start at margin of an atrophic scar [31]. FAF shows a marked hypoautofluorescence in areas of chorioretinal atrophy (**Figure 4**) [24] and OCT-A detects flow reduction at the level of the choriocapillaris which is also the pathophysiology of both SC and APMPPE/AMIC [32].
