Vogt-Koyanagi-Harada disease (VKH) is a chronic systemic autoimmune disease characterized by bilateral, granulomatous panuveitis, as well as skin, auditory, and neurological involvement [6]. Multiple signs associated with VKH on ICGA have been described; however, the most commonly reported sign is small hypocyanescent spots [7]. These hypocyanescent areas have been attributed to choroidal granulomas, are apparent on early to intermediate frames, and often persist to late frames, depending on the thickness of the granuloma [3, 7]. In more advanced cases of VKH, the extent of chorioretinal atrophy can be visualized on ICGA as hypocyanescent areas, typically present throughout the study [7, 8]. Other characteristic ICGA signs that have been noted in VKH include early hypercyanescent stromal vessels, intermediate to late peripapillary hypercyanescence, and late diffuse hypercyanescence [7]. ICGA has also been shown to be useful in assessing the response to therapy and in detecting subclinical posterior disease in anterior uveitis flares [9].

Sympathetic ophthalmia (SO) also presents with a bilateral granulomatous panuveitis and occurs following traumatic injury or surgery to the inciting eye. Inflammation in both the inciting eye and sympathizing eye ensues [10]. The posterior segment findings are similar to VKH, although SO has historically been described as sparing the choriocapillaris. Similarly to VKH, early to intermediate hypocyanescent spots, with variable persistence, are seen [11].

Choroidal granulomas resulting in hypocyanescent spots are also seen in sarcoid choroiditis but are more irregularly distributed [3, 12] (Figs. 2.2 and 2.3).

Birdshot chorioretinopathy (BCR) is characterized by the presence of bilateral ovoid hypopigmented lesions, low-grade anterior chamber and vitreous inflammation, retinal vasculitis, and HLA-A29 positivity [13]. Ovoid or circular hypocyanescent lesions, especially nasal and inferior to the optic disc, are seen on early to intermediate frames, and frequently appear more prominent on late frames [14]. The hypocyanescent lesions have been postulated to be due to non-penetration of the ICG dye at the site of inflammatory choroidal infiltrates [3].

Given that ICG lesions exceed the lesions visible on fundus exam or color fundus photos, ICGA has an important role in the diagnosis of this disease, especially in early presentations of BCR, when the characteristic ovoid lesions may be absent or minimal on examination and FA findings may also be mild [3, 14]. More recently, ICGA is emerging as a useful modality in monitoring the response to immunomodulatory therapy , since a decrease in the number of ICGA lesions with treatment has been reported [4] (Fig. 2.4).

Although acute posterior multifocal placoid pigment epitheliopathy (APMPPE) was originally proposed by Gass to be a disorder of the pigment epithelium [15], APMPPE is now believed to primarily affect the choriocapillaris with secondary retinal epithelium and outer retinal changes [16]. During acute disease, ICGA shows confluent areas of hypocyanescence, evident on all phases, but especially prominent on late frames. These hypocyanescent areas are thought to correspond to hypoperfusion of the choriocapillaris and are typically more numerous than and extend beyond the placoid lesions observed on fundoscopy. Some of these hypocyanescent lesions resolve completely following recovery, while others decrease in size but persist consistent with atrophy [3, 17, 18] (Fig. 2.5).

Multiple evanescent white dot syndrome (MEWDS) is considered to be a self-limiting disease of the outer retina. The fundus examination findings of MEWDS can include posterior vitreous cell, disc hyperemia or edema, small multifocal white lesions involving the posterior pole and mid-periphery, and foveal granularity [19, 20].

The white MEWDS lesions have been classified by size and location into “spots” (larger than 200 μm, localizing to the RPE/photoreceptor junction) and “dots” (smaller than 100 μm, localizing to the outer nuclear layer) [21]. This classification has also been used to apply to FA and ICGA signs [20–22]. On ICGA, hypocyanescent dots have been described on early to mid phase ICGA, which correspond to hyperfluorescent dots on FA [20, 22]. In contrast, hypocyanescent spots observed on mid to late frames correspond to hyperfluorescent spots on FA [20, 22]. In more severe cases, confluent areas of hypocyanescence can be present [3]. Additionally, peripapillary hypocyanescence has also been described in MEWDS. It is now thought that the hypocyanescent areas on ICGA may not be stemming from hypoperfusion of the choriocapillaris [3]. Indeed, this has been corroborated by recent reports showing an absence of choriocapillaris flow voids on OCTA in MEWDS [22]. The cause of the hypocyanescent areas on ICGA remains unclear, although it has been proposed that the hypocyanescent spots may be caused by focal RPE dysfunction [23].

The MEWDS lesions on ICGA are typically more numerous than those apparent on fundus examination or FA. Thus, ICGA, in combination with FAF, is especially useful in mild cases of MEWDS, when only minimal findings are apparent on fundoscopy [3]. In accordance with the transient nature of this disease, ICGA findings usually resolve within 4–6 weeks, in tandem with exam findings and signs on other imaging modalities [3] (Fig. 2.6).

MFC is characterized by variably sized posterior pole and mid-peripheral chorioretinal lesions, as well as the presence of vitreous cell, and often anterior chamber inflammation [24]. In contrast, PIC typically presents without vitreous inflammation, and with smaller-sized lesions (100–300 μm), restricted to the posterior pole [25]. Both entities are associated with choroidal neovascularization [26].