Serpiginous choroiditis (SC) is a chronic and progressive form of posterior uveitis. This condition affects the RPE and the inner choroid and results in progressive visual dysfunction. Typically, SC begins with multifocal choroidal lesions in the peripapillary region that advance in a serpiginous manner and become confluent [4]. Such a phenotype is termed as juxta-papillary choroiditis . Other patterns of SC include placoid chorioretinitis and ampiginous choroiditis . Progressive outer retinal and photoreceptor damage in SC results in visual loss that can be disabling, especially if the lesions involve the macula. The management of idiopathic SC often requires systemic corticosteroids and immunosuppression. Thus, it is important to detect active lesions in the fundus as the disease may demonstrate waxing and waning course of inflammation.

Active evolving SC lesions correspond to the hyper-autofluorescence areas (Fig. 5.2a–d) on FAF [4]. SC lesions undergoing the healing process appear to have a hypo-autofluorescent rim around the central hyper-autofluorescence on FAF showing a rather stable lesion which is not increasing in size. Further resolution of the lesion demonstrates a hypo-autofluorescent stippled pattern on FAF. It is possible to monitor the response of chorioretinal lesions to immunosuppressive therapy by periodic FAF imaging [5].

In a case series of 12 patients, FAF findings showed an evidence of hyper-autofluorescence corresponding to active inflammation, with hypo-autofluorescent halos [6]. Presence of hypo-autofluorescent halo may represent walling off of the inflammation in the early stage of healing. In transitional stage, FA indicates the resolution of active inflammation corresponding to hypo-autofluorescent rim surrounding the hyper-autofluorescent interior on FAF. More advanced stages of healing show SC lesions appearing progressively more hypo-autofluorescent. Thus, SC lesion pattern on FAF correspond to the active inflammation as seen on FA.

In another case series consisting of four patients with juxta-papillary SC, similar findings were noted by the authors [5]. Active lesions appeared hyper-autofluorescent on FAF. Early stage of healing was characterized by a mixed pattern of hypo- and hyper-autofluorescent lesions. This transient phase was followed by homogenous hypo-autofluorescent appearance of the lesions during advanced stages of healing.

In addition, studies have shown a potential association between structural loss of RPE observed on FAF and the functional outcomes in patients with SC. For instance, in one study, visual acuity correlated with the area and fluorescence of SC lesions [7].

In conclusion, FAF has applications in the evaluation of inflammatory disease activity in SC, identification of the phenotype of the disease, extent of tissue involvement, and the progression of chorioretinal lesions in response to therapy.

Birdshot chorioretinopathy (BSCR) is a chronic posterior uveitic disorder characterized by hypopigmented deep yellowish lesions scattered across the posterior pole. While the exact etiology of BSCR still remains unknown, this condition is noted to have a predilection for Caucasian race. Although a causal relationship has not been established, BSCR demonstrates a strong correlation with human leukocyte antigen (HLA)-A29. BSCR is characterized by characteristic “birdshot” chorioretinal lesions that often involve the peripapillary region. In addition, the macular and extramacular regions demonstrate significant abnormalities in various layers of the retinochoroid.

Lesions of BSCR can be effectively studied using FAF. An interesting aspect of BSCR is that the lesions seen on FAF may not necessarily correspond to the chorioretinal lesions observed clinically [8] or on Goldmann visual field [9]. Often, greater extent of chorioretinal pathology may be noted on FAF compared to routine fundus imaging (Fig. 5.3a–d). Such a phenomenon in BSCR may be explained on the basis of greater involvement of outer retina and RPE-Bruch’s complex than choroidal stromal involvement. Therefore, RPE damage may occur early during the course of the disease resulting in greater damage visible on FAF (Fig. 5.4a–d). In their study of 16 eyes with BSCR, Koizumi and colleagues also concluded that clinically observed lesions did not correspond to the hypo-autofluorescent areas seen on FAF. Such a finding indicates that the disease may have differential involvement of the retinochoroid, and thorough assessment of the pathology of BSCR requires multimodal imaging analysis [10].

Thus, FAF is a relevant supplementary tool in the diagnosis and management of patients with BSCR. Further studies that correlate the findings on FAF with other modalities such as visual fields and FA may shed more light on the pathophysiology of this condition.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an idiopathic disorder characterized by placoid grayish-white lesions scattered in the RPE and inner choroid [1]. APMPPE most commonly affects middle-aged men and women and shows bilateral involvement. While the exact pathogenesis of this condition is not known, the disease is known to primarily affect the choriocapillaris and involve the RPE-Bruch’s membrane complex.

Similar to SC, APMPPE also shows increased autofluorescence during the active stage of the disease. On the other hand, hypo-autofluorescence is observed with older and dormant lesions. The APMPPE lesions that appear hyper-autofluorescent on the FAF are also seen to appear hyper-reflective on OCT. Various case studies show that the FAF findings vary from patient to patient. There can be hyper-autofluorescence in the active APMPPE lesions, at the same time hypo-autofluorescence in other active lesions that are obscured by the overlying edema. Similarly, hypo-autofluorescence in the RPE secondary to atrophy and loss of normal fluorophores may be observed [11].

Acute zonal occult outer retinopathy (AZOOR) is a syndrome of loss retinal function in retinal zones secondary to the slow and progressive loss of RPE integrity and function. Vision compromise and blind spot enlargement are also observed in many cases. Patients affected by AZOOR are commonly young myopic women with unilateral followed by bilateral involvement. Significant visual field abnormalities may be detected as the disease continues to progress.

FAF imaging is an important investigation in patients with AZOOR. On FAF, conspicuous areas of central hypo-autofluorescence may be observed that correspond to the atrophy of the RPE and choriocapillaris. Fujiwara et al. in their study (n = 17 eyes with FAF abnormalities) showed that 14 eyes with AZOOR had areas of hypo-autofluorescence whereas the remaining three eyes had mixed hypo- and hyper-autofluorescent areas. Often, the peripheral expanding edge of the lesions demonstrates hyper-autofluorescence due to increased RPE metabolic activity. Gass et al. and Fujiwara et al. in their respective studies also showed a peripapillary hypo-autofluorescence indicating lipofuscin accumulation. In a study correlating FAF with OCT in patients with AZOOR, areas of hypo-autofluorescence corresponded to decreased photoreceptor layer thickness, absent outer nuclear layer, and abnormal photoreceptor inner segment-outer segment junction patterns (of absence or attenuation) [12, 13].

In summary, FAF can provide valuable information in patients with AZOOR and allow detailed assessment of RPE damage in these patients.

Multiple evanescent white dot syndrome (MEWDS) is a rare ocular disorder that presents with distinct small whitish lesions at the level of the RPE and outer retina. On clinical examination, the presence of granular fovea is a characteristic finding. In many instances, the disease is self-limiting warranting no treatment. Although ICG and FA are valuable tools in detecting and identifying the extent of the disease, FAF has recently been proven to be a valuable adjunct that can provide additional information.

Frino et al. [14] demonstrated in three patients, the nature of the lesions on ICG, FA, and FAF imaging. During the active stage, hyper-autofluorescence of the lesions was noticed suggesting ongoing inflammation in RPE.

Dell’Omo et al. [15] observed the natural evolution of the MEWDS lesions using multimodal imaging including FA, FAF, and ICG. In acute or subacute stages of the disease, early hypo-autofluorescence and late hyper-autofluorescence areas can be visualized that correspond to similar brownish lesions on clinical examination, pinpoint leaky lesions on FA with early hypo-fluorescence with late hyper-fluorescence, as well as early hyper-fluorescence with late hypo-florescent lesions on ICG [10]. A rather unusual finding after several months of follow-up of the disease was that two of the total nine eyes had persistent hyper-autofluorescence of the lesions on FAF, with a dramatic improvement in FA and ICG findings [15].