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Although the typical serpiginoid lesion, when present, is distinctive, one needs to be aware that other conditions can simulate the clinical appearance, including tuberculosis.
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Reactivation is typically at the borders of older lesions and will show blockage in the early phase of the angiogram.
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High-dose prednisone or other forms of aggressive therapy can be used to stop the reactivation.
Serpiginous choroidopathy is a clinically defined disorder characterized by destruction of the inner choroid and the retinal pigment epithelium (RPE) as well as secondary involvement of the retina. This entity has been known by a multitude of names, including serpiginous choroiditis, geographic choroiditis, geographic choroidopathy, geographic helicoid peripapillary choroidopathy, and macular geographic helicoid choroidopathy. Although by the early part of the last century it had been recognized as a distinct but poorly defined entity, our understanding of this disease remains limited. We still are not sure whether the retinal destruction seen in serpiginous choroidopathy is mediated predominantly by an inflammatory process or by an abiotrophy. In fact, the clinical spectrum of serpiginous choroidopathy may represent several different diseases. One notion is that it is an extreme form of the white-dot syndromes. Until we know more about these entities, the author prefers not to lump them together. In most uveitis clinics it is a fairly rare entity, comprising no more than 5% of posterior uveitis.
Clinical features
The typical patient with serpiginous choroidopathy is middle-aged and has no major underlying medical problems. Although the disease has been reported in patients of varying ethnic backgrounds, it may be seen more commonly in white persons. In some series there is a slight male preponderance.
Patients usually report blurred vision or a central or pericentral scotoma in one eye, although examination usually reveals bilateral disease. Serpiginous choroidopathy primarily affects the choroid, choriocapillaris, and RPE. The terms serpiginous, helicoid, and geographic describe the appearance of the chorioretinal disease, which progresses in a serpentine fashion, usually starting at the optic disc and winding through the posterior pole ( Fig. 28-1 ). Acute lesions appear gray-white or yellow and involve the choriocapillaris and RPE. On careful examination these new lesions appear to have ‘substance,’ and they subtly elevate the overlying retina. Acute lesions last up to several months, but over time they become atrophic, with disappearance of the choriocapillaris and involvement of the underlying large choroidal vessels. Thinning of the overlying neurosensory retina usually follows disease of the choroid and RPE, and scarring with clumps of RPE are common late in the course of the disease.
Patients rarely have a solitary active lesion involving the posterior pole. Much more commonly, active lesions occur adjacent to an area of choroidal and RPE atrophy. An area of chorioretinal atrophy often can be found next to the optic disc in a symptom-free contralateral eye.
Reports in the literature concerning the inflammatory component associated with the choroidal and RPE lesions of serpiginous choroidopathy vary greatly. Hamilton and Bird, for example, observed no inflammatory disease in the patients they studied. In our experience, however, cellular reaction in the posterior vitreous can occur, especially in patients with acute lesions, and mild vitritis has been reported in about one-third of patients. , Anterior uveitis has also been described in patients with serpiginous choroidopathy, but is more rare. It is important to look for evidence of inflammatory disease, because this finding may help in deciding whether a therapeutic intervention with antiinflammatory agents has a reasonable chance for success (see Chapter 7 ).
Choroidal neovascularization can also occur in serpiginous choroidopathy. Gass stated that choroidal neovascularization occurs in as many as 25% of patients, although we have observed it in fewer than 10% of our patients at the National Eye Institute. Blumenkranz and coworkers reported active choroidal neovascularization in seven of 53 patients with the disease. Choroidal neovascularization may be seen at the time the disease is diagnosed, and when located in the macula may cause a visual disturbance ( Fig. 28-2 ). Although the choroidal neovascularization may regress spontaneously in some patients, we have treated membranes threatening the fovea with laser photocoagulation. Serous detachments of the neurosensory retina, as well as RPE detachments, have been reported in patients with serpiginous choroidopathy. , Retinal vasculitis may also occur, and branch vein occlusions have been reported. ,
The disorder usually begins near the disc, with new areas of activity being evident at the margin of old lesions. This centripetal or helicoid extension can continue for years. Laatikainen and Erkkilä followed 15 patients for a mean of 4.9 years and noted new lesions in eight. These acute lesions can cause a decrease in visual acuity that may return after a long recovery period. Weiss and coworkers observed that visual acuity decreased in nine of 17 eyes after an acute episode, and that the visual acuity returned to the preattack level once the acute lesions resolved, although this could take a number of months. They further noted that 15 of 17 eyes ultimately developed lesions involving the fovea, although Laatikainen and Erkkilä noted a loss of central vision in only six of 28 eyes.
The diagnosis of serpiginous choroidopathy is made purely on clinical grounds, with the major criteria listed in Box 28-1 . Fluorescein angiography and serial fundus photographs are also helpful in following the disease. Fluorescein angiographic examination of an active lesion will show early blockage with late hyperfluorescent borders that spread toward the center of the lesion ( Fig. 28-3 ). The early hypofluorescence of active lesions may be due to blockage of the underlying choroidal fluorescence by swollen RPE cells, but more likely represents the impaired choroidal vasculature. Old atrophic lesions will show diffuse staining, and hyperfluorescence is noted in areas of RPE clumping. Late staining of the retinal vessels is seen in patients with a vasculitis or perivasculitis. There have been several reports describing the use of indocyanine green (ICG) angiography to evaluate this disorder. What seems to be a recurring theme is that although fluorescein angiography appears to be more effective for showing active and inactive lesions, ICG methodology usually demonstrates many more lesions than are seen with fluorescein. Therefore, the use of ICG methodology may help to better describe the extent of the disease, even before it is seen with fluorescein angiography. It can help the observer to determine the ultimate clinical progression of the disease. Fundus autofluorescence can be used in addition to OCT and ICG observations. In one study reported by Cardillo-Piccolino and colleagues, autofluorescence, OCT and ICG were used to follow the course of disease in two patients with serpiginous choroiditis. They found that the fundus hyperautofluorescence was noted 2–5 days after the appearance of the clinical lesion, delineating what could be the area of real RPE damage, as this area was smaller than the defects seen on ICG. As the disorder became quiescent, these same areas showed hypoautofluorescence, whereas the OCT still demonstrated lesions in the photoreceptor region.
Patient
White
Both genders
Late teens to 60s
Ocular examination
Inflammatory response in the anterior chamber or vitreous sometimes occurs
Lesion begins in the peripapillary region; centripetal or helicoid progression, giving ‘geographic’ distribution
New white-yellow lesions begin at edge of old ones
Bilateral involvement
Additional tests
Fluorescein angiography
Serial fundus photographs
It is probably fair to say that the appearance of the lesions we recognize as serpignous choroiditis is not a single disease but also can be a manifestation of infectious processes. Although most patients with serpiginous choroidopathy have no associated medical illnesses and therefore are treated with immunosuppressive agents, it has become clear through several reports that a careful medical evaluation is critical to rule out an underlying infectious process.
Pathology
Unfortunately, few eyes with serpiginous choroidopathy have been studied in the pathology laboratory. Histologic examination shows an extensive loss of the RPE and destruction of the overlying retina. Portions of the choriocapillaris and part of the choroid are filled with a lymphocytic infiltrate, suggesting that the disease has an inflammatory component ( Fig. 28-4 ). , Areas of RPE hypertrophy and subretinal scarring have also been described. An eye evaluated for the presence of virus (see below) showed a lymphocytic infiltration as in the previous case. On the basis of these few observations it would seem reasonable to consider this lesion a choroiditis.
Etiology
The cause of serpiginous choroidopathy is unknown. It had been suggested that the disorder is the result of a vascular abiotrophy and should therefore be considered degenerative. Laatikainen and Erkkilä indicated that an immune-mediated vasculitis might induce occlusion of the choroidal vessels. The finding of a lymphocytic infiltrate in the choroid and an accompanying vitritis suggests an inflammatory etiology. In one study the incidence of HLA-B7 was higher in 15 Finnish patients with serpiginous choroiditis than in the control group (54.5% versus 24.3%, p <0.05). In addition, increased levels of antibacterial antibodies, such as antistreptolysin O, were found in eight of the patients with serpiginous choroiditis. The clinical course of the disease, characterized by multiple recurrent inflammatory episodes, is compatible with an infectious disease process such as herpes virus infection. Serpiginous choroidopathy has been reported after viral meningitis, and some clinicians give anecdotal reports of improvement after treatment with aciclovir. Nevertheless, firm evidence to suggest an infectious cause is lacking. Indeed, in a report by Akpek and colleagues, using the polymerase chain reaction (PCR), no evidence of herpes simplex virus (HSV) P1/P2 (for HSV-1, HSV-2, Epstein–Barr virus [EBV], cytomegalovirus [CMV] and human herpes virus [HHV]-8), and varicella-zoster virus (VZV) P1/P2 (for VZV, HHV-6, HHV-7) can be demonstrated in the infiltrating lymphocytes or the choroidal tissue. Theoretically it is possible that the the inflammatory disease may be a secondary phenomenon unrelated to previous infection that may have originally been directed against a viral antigen. Retinal degeneration after the impairment of the choroidal vasculature could release potentially antigenic moieties, which in genetically prone persons leads to an inflammatory response.
Differential diagnosis
A number of disorders should be considered in the differential diagnosis of serpiginous choroidopathy. Several authors have reported the association of serpigninous-like lesions associated with tuberculosis. Gupta and Gupta reported seven patients in India with choroidal tuberculosis that presented as what clinically appeared to be serpiginous choroditis. The clincial presentation included multifocal lesions that progressed to a wavelike confluence; others were plaque-like with an ameboid presentation. Teyssot and coworkers emphasized the need to evaluate their French patients with all types of disorder at the level of the retinal pigment epithelium/choroid/choriocapillaris. In 14 patients with disorders at that level of the eye, six (including those with serpiginous choroidopathy) had a family history of tuberculosis or active infection. Recently Mackensen et al. performed a retrospective evaluation of German patients with a serpiginous-like choroiditis. Eleven of the 21 patients tested for tuberculous exposure using the QuantiFERON test were positive. Many of these were known to have had positive Mantoux skin tests; 13% of other uveitis patients tested positive. All of this emphasizes how important a thorough evaluation is. Tuberculosis may also explain the relatively high percentage (19%) of serpiginous patients seen in a large uveitis center in India. Other infectious processes have been reported to present with a serpiginous-like lesion as well. Such an example is a 32-year-old woman who presented with blurred vision in her left eye. The ocular examination revealed extensive serpiginoid lesions. Blood serology and PCR performed on aqueous from her eye were both positive for toxoplasmosis ( Fig. 28-5 ).
Noninfectious disorders may present with similar clinical findings to serpiginous choroiditis. Posterior scleritis may mimic a macular serpiginous lesion, though this is associated with pain ( Fig. 28-6 ). The bilateral lesions of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) may appear similar to those of serpiginous choroidopathy. Acute lesions in both diseases may be yellowish and involve the choroid and retina at the level of the RPE, and RPE clumping can be seen late in the course of both diseases ( Fig. 28-7 ). Acute lesions of both APMPPE and serpiginous choroidopathy show early blockage of fluorescence and late hyperfluorescence. However, the acute lesions of APMPPE resolve within 2 weeks, and recurrence is uncommon. In addition, choroidal atrophy and choroidal neovascularization are atypical in APMPPE but common in serpiginous choroidopathy, and the prognosis for good visual outcome is far better for patients with APMPPE. Nevertheless, we have seen a number of patients with a disease that falls between the classic findings of serpiginous choroidopathy and those of APMPPE. We have informally termed this condition ampiginous choroidopathy because these patients have fundus lesions typical of those seen in APMPPE but develop recurrent disease more typical for the patient with serpiginous choroidopathy ( Fig. 28-7 ). They do, however, maintain relatively good central vision and do not have the relentless, helical progression characteristic of serpiginous choroidopathy. However, large portions of the retina may be involved. Jones and colleagues described a condition similar to the one we have described with a prolonged progressive clinical course and widespread lesions. Perhaps a variant of ampiginous is what has been termed persistent placoid maculopathy, which presents as a macular choroiditis ( Fig. 28-8 ) and with many eyes developing choroidal neovascularization (this is described in the chapter on white-dot syndromes).
