Inflammation of the optic nerve is a very common but non-specific sign of active intraocular inflammation manifested clinically as hyperemia, absence of the cup, and a variable degree of blurring of the disc margin (Table 1.3). Hyperfluorescence of dilated disc capillaries is visualized early on FA as late staining of the optic disc with the extent of disc margin obscuration depending on the degree of dye leakage (Fig. 1.1a, b). Optic disc inflammation as seen on FA uniformly accompanies uveitic macular edema (ME) and, is useful in distinguishing it from noninflammatory causes of ME and from other forms of optic disc involvement such as neuroretinitis . Subtle optic nerve hyperfluorescence may denote subclinical inflammation and be useful as a sign of active disease and in monitoring the response to anti-inflammatory treatment.

Macular edema is the leading cause of central visual loss among patients with uveitis [10, 11]. Inflammatory macular edema is thought to arise from the breakdown of the inner blood retinal barrier mediated by inflammatory cytokines leading to increased vascular permeability of the perifoveal capillaries and the accumulation of fluid within in the outer plexiform layer and sub-neurosensory retina [12]. Angiographically, there is corresponding late leakage and pooling of fluorescein dye into these spaces with the characteristic pattern of petaloid hyperfluorescence together with optic disc staining (Table 1.3) (Fig. 1.2). Several studies have demonstrated that OCT , a noninvasive, quantitative, reproducible modality for the measurement of retinal thickness, can be as effective as FA in demonstrating ME in patients with uveitis with visual loss correlated with central macular thickness and the severity of leakage [13–15]. However, it is important to note that FA and OCT measure different manifestations of an underlying inflammatory disease, the pathophysiologic process of vascular leakage, and the anatomic changes in retinal thickening (or thinning), respectively. Leakage seen on FA may not always be accompanied by an increase in macular thickness on OCT (Fig. 1.3a, b). Conversely, macular thickening may occur in the absence of ongoing vascular leakage with RPE pump dysfunction in the presence of chronic intraretinal or subretinal fluid. OCT may be the best test for the initial detection and longitudinal monitoring of inflammatory ME; however, compensated leakage may be present in the absence of retinal thickening and vice versa.

Clinically, retinal vasculitis appears as perivascular, creamy-colored cuffs with varying degrees of exudation and sheathing (Table 1.3). The pattern, type, extent, and location of retinal vascular staining and leakage may be useful diagnostically (Tables 1.4, 1.5 and 1.6). In addition, FA is essential for the identification and treatment of vasculitic complications such as retinal nonperfusion, neovascularization, telangiectasia, arterial-venous (AV) anastomosis, and micro- and macroaneurysms. As with inflammatory ME, staining and leakage of the vessel walls are sensitive indicators of inflammatory activity, such as in asymptomatic patients with pars planitis or BSRC in the absence of clinically apparent signs and in vitrectomized eyes in which the usual surrogate markers of activity (vitreous cells/haze) may have been removed. Finally, FA is indicated in the evaluation and management of systemic diseases with retinal vascular involvement such as Behçet’s disease (BD) , ANCA-associated vasculitides , Susac’s syndrome , and systemic lupus erythematosus (SLE) [16].

Uveitic entities commonly associated with retinal phlebitis and the corresponding FA findings are described in Table 1.4. In sarcoidosis-associated periphlebitis , the pattern of vascular staining and leakage is characteristically segmental or discontinuous and may be associated with yellow perivascular exudates described as “taches de bougie” (candle wax drippings) (Fig. 1.4). In contrast, a more diffuse pattern is observed in idiopathic retinal vasculitis and with CMV-associated frosted branch angiitis [17] (Fig. 1.5). Retinal vascular involvement in pars planitis is common and may exhibit both segmental and diffuse staining and leakage of the veins with small vessel hyperfluorescence in a characteristic “fern pattern” (Fig. 1.6) [18–21]. Wide field imaging may reveal more extensive peripheral vascular staining and leakage than that visualized on conventional FA, particularly when posterior pole involvement is absent [22, 23]. In the management of BSRC, FA reveals critical components of disease activity including the extent of periphlebitis and optic nerve leakage which may not be appreciated on clinical exam (Fig. 1.7a, b).