Diagnostic Criteria

In 2002, Gass described diagnostic criteria of AZOOR as follows (Gass et al. 2002): acute visual field or vision loss usually with concurrent photopsia, one or more visual field defect regions that could not be explained by funduscopic examination or fluorescein angiography (FA), and decreased amplitude on ERG. ERG is an important tool for the diagnosis of AZOOR because it can detect functional loss of the photoreceptor. Multifocal ERG is especially useful because it can focally detect depressed amplitudes in the AZOOR-affected area (Arai et al. 1998).

In 2007, Li reported that SD-OCT revealed loss or discontinuity of the ellipsoid zone (EZ) corresponding to the AZOOR lesion sites (Li and Kishi 2007). Since then, SD-OCT evidence of outer retinal morphological abnormalities has become an important tool for the diagnosis of AZOOR (Spaide et al. 2008). Thus, it is important to verify morphological and functional photoreceptor impairments via both SD-OCT and ERG to obtain a diagnosis of AZOOR and to rule out other diseases, such as infectious chorioretinitis (e.g., syphilis and tuberculosis) and cancer-associated retinopathy.

Etiopathogenesis

The mechanism that causes photoreceptor impairments in AZOOR remains unclear. Approximately 30% of patients with AZOOR have systemic autoimmune diseases (Gass et al. 2002; Hintzen and van den Born 2006). Systemic corticosteroid therapy appears to be effective for patients with AZOOR (Saito et al. 2014, 2015; Kitakawa et al. 2012; Chen et al. 2015). These observations suggest that AZOOR has an autoimmune/inflammatory mechanism. At present, two opinions on the etiology of AZOOR are under consideration. One is the anti-retinal antibodies (ARAs) theory because recent studies have reported that serum ARAs are high in patients with AZOOR (Tagami et al. 2014; Qian et al. 2017). However, ARAs might be secondarily produced following retinal impairment caused by AZOOR (Forooghian 2017), because there is no evidence of an association between ARAs and the pathogenesis of AZOOR.

The other theory pertains to choroidal impairment because the photoreceptors receive a supply of oxygen and nutrition from the choriocapillaris. In patients with AZOOR, macular choroidal blood flow velocity is increased, and choroidal thickness decreased when visual function and outer retinal morphology improved (Saito et al. 2014; Hashimoto et al. 2017). This circulatory and morphological pattern is consistent with that of choroiditis, for example, Vogt–Koyanagi–Harada disease and serpiginous choroiditis (Hirooka et al. 2015; Takahashi et al. 2014). Moreover, other AZOOR complex diseases, MEWDS, PIC, and AMN show the same pattern (Hashimoto et al. 2015, 2016, 2019; Hirooka et al. 2014a, b). Therefore, these results suggest that inflammatory choroidal circulatory impairment is involved in the common pathogenesis among AZOOR complex diseases including AZOOR. However, these observations might be secondary to damaged photoreceptors (Fagan 2014). Thus, further studies are needed to verify whether either of the two AZOOR theories is correct.

Clinical Features

Symptoms and Ocular Findings

Patients with AZOOR have an acute onset of one or more zones of visual field defect with or without loss of visual acuity. Moreover, they often complain of photopsia such as flickering and whirling within the regions of the visual field defect, which is a characteristic of AZOOR. Relative afferent pupillary defect is present in 24% of the affected eyes (Gass et al. 2002), and patients with this finding may often be misdiagnosed with retrobulbar optic neuritis. Inflammatory cells are not present in the anterior chamber but may be present in the anterior vitreous. The presence of vitreous cells is associated with large visual field defects at the initial visit (Gass et al. 2002; Saito et al. 2015). In most cases, the initial appearance detected by funduscopic examination is normal (Fig. 6.1). Abnormal findings such as a few punctate atrophic scars, which are unrelated to the AZOOR-affected sites, may be present. A white demarcation line at the margin of the lesions and retinal vascular changes such as perivascular sheathing may also be observed (Gass et al. 2002; Mrejen et al. 2014). The affected retinal area later develops a zonal area of RPE degeneration in cases with no or little improvement of visual function (Fig. 6.2). This appears to occur more frequently in Caucasian patients than in Japanese patients (48% vs. 10%) (Gass et al. 2002; Saito et al. 2015). On perimetry tests, an enlargement of the blind spot is commonly detected, often with sparing of central sensitivity (Fig. 6.3) (Gass et al. 2002; Saito et al. 2015). In addition, various scotomata, such as central scotoma, ring scotoma, arcuate scotoma, and hemianopia may be present.

Fundus Angiography

In most cases, fluorescein angiography reveals no abnormalities in the acute stage of AZOOR. In some cases, retinal vasculitis or staining of the optic disc will be present (Fig. 6.4). In the convalescent stage, a window defect is observed corresponding to RPE atrophy. On indocyanine green angiography, abnormal findings such as hypofluorescence in areas related or unrelated to the lesions (Fig. 6.5), diffuse choroidal hyperfluorescence in the middle or late phases, and hyperfluorescence along with large choroidal vessels have been previously reported (Saito et al. 2007, 2015; Monson and Smith 2011).