An autoimmune, infective, vascular, or degenerative etiology has been proposed but no cause has been identified with certainty. Mycobacterium tuberculosis [5, 6] and herpes virus [7] are infective causes which have been reported.

Presentation may be with blurred vision, metamorphopsia, or central and paracentral scotoma. Visual loss depends on the involvement of the macula.

Peripapillary [8] is the typical form and the active stage has a characteristic geographic pattern radiating outward in a serpentine fashion (Fig. 18.1). This centrifugal spread may involve the macula. Recurrences are common and occur from the edges of the previous scars. Lesions are self-limiting. Chronic inflammation can cause pigmentary clumping and atrophic patches in the retina with visibility of choroidal vasculature.

The macular variant of serpiginous choroiditis causes early symptoms due to foveal involvement or due to complications such as CNVM (Fig. 18.2).

Lesions in ampiginous choroiditis [10] appear to represent an intermediate between serpiginous choroiditis and APMPPE. They are bilateral and share similar angiographic features to serpiginous choroiditis and are multifocal as in APMPPE. Ocular tuberculosis forms the essential differential diagnosis in endemic areas.

OCT shows a disruption of the outer retinal architecture, with loss of the junction of the inner and outer segments of the photoreceptors and variable thinning/thickening of the RPE-Bruch’s membrane layer, corresponding to the scars.

The most frequently considered differential diagnosis is tubercular serpiginous-like choroiditis [16]. However, these lesions have more vitritis and the multifocal lesions lie adjacent to retinal vessels. Investigations are required to confirm the diagnosis. APMPPE, multifocal choroiditis with panuveitis, and outer retinal toxoplasmosis may also need to be considered while making a diagnosis.

Direct involvement of the macula by an active lesion can cause visual loss. In the healed stages, choroidal neovascular membranes or scarring can occur. The most common cause of visual loss is CNVM that develops as a result of recurrent attacks. Less frequent complications are branch retinal vein occlusion, periphlebitis, serous retinal detachment, cystoid macular edema, or subretinal fibrosis.

Complete blood count, Mantoux test, syphilis serology serum angiotensin-converting enzyme, and chest radiographs need to be done in all patients. Polymerase chain reaction (PCR), QuantiFERON-TB Gold test [17], nested PCR [18], or real-time PCR [19] can be done to confirm the diagnosis and to exclude infective and systemic causes of posterior uveitis. They can be performed on aqueous [20] or vitreous samples and chorioretinal biopsies.

Factors to be considered are the activity of the lesion and macular involvement. Long-term follow-up is required to monitor response to treatment and to detect recurrence.

Oral prednisolone in the dose of 1 mg/kg/body weight can be given alone or in combination. In patients with macular involvement, intravenous methyl prednisolone is administered in the dose of 1 g for 3 consecutive [21] days to hasten the resolution of serpiginous choroiditis.

The current management modality is a combination of cyclosporine, azathioprine, and prednisolone.

Cyclophosphamide and biological therapy such as interferon alpha-2a [26] are other treatment options.

The exact etiology is unknown, but several associations have been reported including HLA-B7 and HLA-DR2 genetic haplotypes. Approximately 33 % of patients have a preceding viral illness prior to symptom onset which may be associated with meningeal symptoms. APMPPE has also been described in cases of thyroiditis, erythema nodosum, Wegener’s granulomatosis, polyarteritis nodosa, nephritis, sarcoidosis, and CNS vasculitis. Other infectious associations include Lyme disease, mumps, and tuberculosis. Exudative retinal detachment, disk hyperemia, and episcleritis may occur in association [29]. Cerebral vasculitis has been associated with APMPPE and requires treatment with systemic corticosteroids [30].

It is believed to be due to inflammation at the level or the choriocapillaris leading to hypoperfusion and ischemia of the RPE and photoreceptors. In later stages, the inflammed choroid and retina is replaced with RPE atrophy and hyperpigmentation.

Patients present with rapid loss of vision or less frequently with photopsias and central and paracentral scotomas. The symptoms are usually bilateral but asymmetric. Visual acuity depends on the extent of foveal involvement and visual loss is transient.

Anterior segment is normal and there may be mild vitritis. Fundus examination shows multiple bilateral yellow-white placoid lesions at the level of RPE and choroid 1–2 disk diameters in size located in the postequatorial region (Fig. 18.3). The lesions gradually fade over the course of 1–2 weeks. New lesions may appear in the periphery up to 3 weeks following onset (radially or linearly). Older lesions are replaced with RPE atrophy or hyperpigmentation. Disk edema, retinal vasculitis, and venous occlusions may be present. Exudative retinal detachment, disk hyperemia, and episcleritis may occur [29]. Systemic associations have been described with APMPPE including meningoencephalitis, nephritis, and hearing loss. Fatal cerebral vasculitis has rarely been associated with APMPPE.

APMPEE is self-limiting and has a good prognosis. Visual acuity is diminished very profoundly in the early phases of the disease in some cases but recovers nearly completely to near normal levels. All patients with a new diagnosis of APMPPE should receive a full neurologic and systemic workup to evaluate for CNS vasculitis, sarcoidosis, and tuberculosis. Steroids are used if macular involvement is present as prompt use of systemic steroids resolves lesions rapidly. Cytotoxic therapy with cyclosporine and biologics [34] are used in the treatment of severe neurological disease if present. APMPPE resolves spontaneously in 2–12 weeks and does not usually require treatment. Intravitreal triamcinolone acetonide [35] improved macular anatomy, visual acuity, and macular sensitivity.

Some patients may have difficulty with reading due to persistent scotomas in the central field. Pigmentary alterations may remain after the resolution of the placoid lesions. Recurrences are rare as is choroidal neovascularization.

Presentation is in middle age with preponderance in women with decreased visual acuity, color vision, floaters, and nyctalopia. Anterior chamber is quiet but vitritis is typical. Oval, creamy lesions, ¼ to ½ disk diameter in size, are scattered in the posterior pole (Fig. 18.4). Fluorescein angiography shows hypofluorescence in the early phase and hyperfluorescence in the late phase. Indocyanine green angiography reveals well-delineated hypofluorescence choroidal spots in the midphase of the study which are far more numerous than those seen on either fluorescein angiography or clinically [37]. Optical coherence tomography (OCT) shows photoreceptor atrophy in several areas of both eyes with RPE degeneration beneath the areas of photoreceptor involvement [38]. Fundus autofluorescence [39] imaging shows hypoautofluorescence in areas of RPE atrophy that are more numerous and not uniformly correspondent with the birdshot lesions. Visual fields show progressive loss during the course by both Goldmann and automated (30-2) methods [40]. Electroretinography (ERG) is a useful tool to both diagnose and assess the response to therapy [41]. In specific, the 30-Hertz photopic ERG shows delayed implicit time and decreased signal amplitudes and this abnormality has been observed in 70% of patients at baseline. Apart from cone B wave implicit times, dim rod scotopic amplitudes are also significantly attenuated and decline continues with progression of the disease.

Sarcoidosis, pars planitis, VKH syndrome, sympathetic ophthalmia, and POHS.

The etiology of multifocal choroiditis is unknown; however, some propose that antigens in the retinal photoreceptors and retinal pigment epithelium become sensitized by an exogenous pathogen. There have been systemic associations of multifocal choroiditis including Epstein-Barr virus infection [49]. Multifocal choroiditis with panuveitis (MCP), PIC, and subretinal fibrosis and uveitis syndrome (SFU) represent a subset of white dot syndromes and are viewed as a single disease with a variable severity spectrum. Uncertainty also remains regarding the classification of multifocal choroiditis, punctate inner choroidopathy, and diffuse subretinal fibrosis as separate diseases or a spectrum of the same disease [50].

Patients typically present with decreased vision, photopsias, and enlarged blind spot [51].

Vitritis is present in all patients and may be associated with iridocyclitis. The classic lesions of multifocal choroiditis are 50–350 μm, punched-out chorioretinal scars with pigmented borders in the posterior pole. Acute lesions are typically yellow-white and located at the outer retina and choroid. They may number up to several hundred throughout the retina and they can occur in linear clusters or streak lesions as well. As these lesions age and become inactive, they become atrophic and punched-out. Over time, peripapillary scarring and atrophy may develop, and peripapillary and macular choroidal neovascularization may develop. Cystoid macular edema may be associated with acute lesions, while choroidal neovascularization may be associated with the juxtapapillary scars and deep macular scars [52].

Cystoid macular edema and choroidal neovascularization cause vision loss. Retinal pigment epithelium metaplasia and fibrous scarring are rarer causes of vision loss. Secondary CNVM is very common in patients with MCP and is a frequent complication in up to 33 % of patients [56].

The diagnosis is made by clinical examination but other entities must be ruled out with appropriate laboratory testing [57] and imaging studies [58]. Multifocal choroiditis has a waxing and waning course. These patients require long-term follow-up and visual prognosis is variable. Early in the course of the disease, systemic or periocular steroids are effective in controlling the disease. Late disease stages that include choroidal neovascularization and subretinal fibrosis require immunosuppressive agents for better control. Laser photocoagulation, photodynamic therapy, and anti-VEGF treatment are useful for CNVM. A comparison of bevacizumab versus photodynamic therapy for CNVM in MCP showed greater beneficial effects of visual acuity and central macular thickness in the bevacizumab group [59]. If there is extensive fibrosis that occurs with this syndrome, this may spill over into the development of progressive subretinal fibrosis and uveitis syndrome.

PIC was considered to be a variant of multifocal choroiditis and panuveitis (MFCPU) or a form of limited myopic degeneration. The primary etiology of this inflammatory condition remains unclear, but an association with Epstein-Barr virus [63] and with HLA-DR2 positivity [64] has been reported.

The commonest reported initial symptoms are unilateral scotoma and blurred vision. The patient may be asymptomatic or present with scotoma. Acute loss of vision, however, could suggest choroidal neovascularization.

The disease is self- limited and is seen more frequently in myopic women with age range of 24–52 years [65]. Typical lesions are bilateral, multiple, small, well-defined, yellow-white, usually 100–200 μm diameter, and limited to the posterior pole. Lack of flare and inflammatory cells in the anterior chamber or vitreous cavity [66] is typical. The lack of vitreous inflammation is a hallmark of PIC and the presence of vitritis should suggest a different diagnosis [67]. They progress to atrophic scars, leaving a halo of depigmentation and are deeper and appear punched-out. Choroidal neovascular membranes occur in between 40 and 75 % of patients [68].

OCT shows attenuated signals of photoreceptor inner/outer segment areas corresponding to the visual field defect and increased choroidal thickness [70]. Spectral-domain OCT characterized a 5-stage evolution of PIC lesions as choroidal infiltration, formation of sub-RPE nodules, and then chorioretinal nodules, regression, and retinal herniation [71].

Imaging of patients with MFC/PIC reveals extensive pathology beyond the clinically apparent spots. FAF findings highlight the areas of corresponding anatomic disruption of the photoreceptor–retinal pigment epithelium complex [72] and help to assess the resolution of the disease by the appearance of the RPE [73].

CNVM and subretinal fibrosis. CNVM is the most common cause of visual loss in PIC. No differences were observed between eyes with typical and atypical choroidal lesions, supporting the notion that they represent a spectrum of a single disease, PIC [74].

The multifocal dots in the posterior pole may resemble presumed ocular histoplasmosis, APMPPE, Behcet’s disease, Harada disease, leukemia, myopic degeneration, multiple evanescent white dot syndrome (MWEDS), pars planitis, sarcoidosis, sympathetic ophthalmia, serpiginous choroiditis, Vogt-Koyanagi-Harada disease, or Whipple’s disease.

No treatment is advised for the majority of patients with PIC when there is no evidence of CNV as the visual prognosis is excellent.