Pathogenesis of this condition remains unknown despite many studies attempting to identify infectious or autoimmune etiologies. An autoimmune etiology has been proposed and supported by the presence of anterior uveitis, vitritis, and the resolution of lesions when treated with corticosteroids and other anti-inflammatory agents. A vasculopathy has also been suggested but most patients do not manifest systemic vascular abnormalities. An association with tuberculosis exposure and herpes viruses has also been considered as potential predisposing factors but this remains to be proven.

On FA, serpiginous choroiditis demonstrates early hypofluorescence secondary to the atrophy of choriocapillaris and progressive hyperfluorescence at the margin of the lesions. The active lesions, usually at the borders of old lesions, block fluorescein early and show diffuse staining and leakage progressively in the later frames.

In the acute stage of serpiginous choroiditis, the lesions show an ill-defined halo of increased (Fundus Autofluorescence) FAF giving a diffuse, amorphous appearance.

ICG angiography is characterized by geographically confluent or patchy hypofluorescent areas with irregular shapes and indistinct borders beginning from early to the late phase and either remain hypofluorescent or become isofluorescent in the late phase. ICG can be helpful in disclosing active subclinical lesions [17].

Visual fields demonstrate absolute and/or relative scotomatas corresponding to the geographic lesion and as lesions resolve, scotomas can become less dense. The role of OCT is complementary to the other modalities of testing mentioned above.

The natural history of the condition is one of multiple recurrences and progressive scarring that can eventually involve the posterior pole and the fovea with poor visual outcome. Often, when patient have symptoms, the lesions are already in the fovea and at this stage, usually there is significant scarring and high risk of permanent vision loss. The role of any successful treatment is to control the active lesions rapidly and prevent further recurrences and subsequent progression of the disease.

The use of corticosteroids can be effective in controlling the active lesions but they have no effect on the prevention of recurrences, hence it does not alter the natural course of the disease and the final visual outcome. Cyclosporine has been used with mixed results. In one series with seven patients, the treating physician used oral cyclosporine (3–5 mg/kg/day) for a duration of 1.3–5 years (median 3 years). No patient in this series had significant vision loss, and six of the seven achieved remission and were able to stop medications without recurrence [18]. Combination therapy consisting of cyclosporine, azathioprine, and prednisolone has also been described. This combination of agents induced rapid control of ocular inflammation and promoted visual recovery, but some patients had a relapse upon tapering the medications and others required protracted duration of therapy to maintain quiescence.

The efficacy of antimetabolites (methotrexate, mycophenolate mofetil, and azathioprine) in serpiginous choroiditis has been documented in multiple case series. Similarly, alkylating agents such as cyclophosphamide and chlorambucil are effective in rapidly controlling the inflammation and inducing drug-free remission. Without large multicenter trials, it is difficult to determine the best treatment strategy for these patients [16].

A related entity described as Relentless Placoid Chorioretinitis (RPC) (also known as ampiginous choroiditis) shares typical findings of both APMPPE and serpiginous choroiditis but with an atypical distribution of retinal lesions and different progression of the disease. On exam, patients have bilateral posterior creamy white lesions at the level of the RPE that are usually smaller in size (half disk area) compared to APMPPE, and have involvement anterior and posterior to the equator. Eventually, the lesions may become numerous (>50 lesions) and can be active in both eyes synchronously [19]. The clinical course of RPC tends to be prolonged with persistent lesions that evolve and may recur. Due to the scarcity of cases, the most effective treatment is unknown but prognosis is generally favorable with immunosuppressive strategies (as detailed in the management of serpiginous).