eMedicine Specialties > Ophthalmology > Choroid
Multifocal Choroidopathy Syndromes
Updated: Jan 28, 2010
Introduction
This group of rare disorders involves a primary pathologic process occurring at or near the level of the retinal pigment epithelium (RPE) with or without choriocapillaris involvement. Ultimately, the etiology is presumed to be either a vasculitic obstruction of the choriocapillaris with secondary infarction of the overlying RPE or, possibly, an immunologic response directed at the RPE itself. Many clinical features of these individual entities overlap, causing much confusion. Whether these conditions represent distinct entities or whether some may be parts of a spectrum of the same basic disease is still unknown.
Other conditions of choroiditis with overlying RPE involvement are not described in this article; yet, they are important to consider in the differential diagnosis of these more atypical choroiditides, such as tuberculosis, histoplasmosis, syphilis, posterior scleritis, reticulum cell sarcoma, lymphoid neoplasia, diffuse unilateral subacute neuroretinitis (DUSN), and Lyme disease, or the more common idiopathic syndromes, such as central serous retinochoroidopathy, sarcoidosis, Vogt-Koyanagi-Harada syndrome, and sympathetic ophthalmia.
Classification
Attempts at grouping these myriad disorders, especially by Gass, have resulted in inclusion of multiple evanescent white dot syndrome (MEWDS), acute idiopathic blind spot enlargement syndrome (AIBSES), acute macular neuroretinopathy (AMN), and multifocal choroiditis (MFC) or pseudo–presumed ocular histoplasmosis (pseudo-POHS) under the term acute zonal occult outer retinopathy (AZOOR)1 . This inclusion group arose primarily from the observation of a few case reports where 2 or 3 of these entities had coincident manifestation in the same patient2 .
AZOOR is characterized by the following common clinical features: minimal initial ophthalmoscopic changes, followed later by signs of retinochoroidal degeneration, rapid reduction in one or more parameters of the visual field, photopsia, and abnormalities on electrophysiologic testing3 .
More recently, AIBSES has been characterized to have sufficiently unique clinical features, such that, despite some similarities to MEWDS, treating it as a distinct and separate entity may be wise4,5,6,7,8 . AMN, a bilateral condition affecting otherwise healthy young adults, appears to involve a pathologic process occurring more in the middle and outer retinal layers rather than in the RPE and choriocapillaris9 . As such, both AIBSES and AMN will not be discussed in this article.
There remains the conviction that the aforementioned entities are sufficiently distinct as to preclude any effective single inclusion group10 . In the absence of any significant histopathologic and serologic findings, these conditions not only continue to present a problem as far as classification, but also remain poorly understood with regards to etiology or pathogenesis. The discussion of the various multifocal choroidopathy syndromes in this article will consider each entity separately and, in so doing, will avoid the thorny issue of endorsing any one classification.
Multifocal Choroiditis
Multifocal choroiditis and panuveitis
Since the initial description of the disease by Nozik and Dorsch in 1973, hundreds of patients have been reported in the literature with multifocal choroiditis and panuveitis (MCP)11 . As mentioned earlier, many investigators have lately suspected that MCP is one and the same with several other disorders, all representing various stages of the same basic clinical entity (ie, AZOOR). With further follow-up of some of these patients, hopefully, this spectrum of clinical manifestations of multifocal choroiditis will become better defined.
The disease affects otherwise healthy young patients in their third decade (average age, 34 y; range, 6-74 y), with an incidence of bilateral involvement of 80%12 . A moderate racial and gender predisposition exists, with approximately 66% of patients being white and 80% of patients being female12 . As well, myopia is present in more than 85% of these individuals.
Signs and symptoms
The principle presenting symptom is usually blurry vision with or without photophobia. Mild ocular pain may occur, accompanied by complaints of metamorphopsia, floaters, scotomas, and photopsia.
Presenting visual acuity may vary from 20/20 to light perception, with an average of 20/100. Clinical examination reveals a mild-to-moderate aqueous inflammation with cell and flare in approximately 50-60% of patients. Small- to medium-sized keratic precipitates may be present, as well as posterior synechiae and iris atrophy with nodule formation. Vitreous cellular infiltrates are present in more than 90% of patients.
As demonstrated in the image below, fundus examination reveals multiple, small, discrete yellow/gray-white spots that are typically round and may be polygon or oval in shape. These lesions are approximately 200 µm in diameter, but they can vary in size (50-1000 µm). The lesions tend to scatter predominantly in the periphery rather than in the macula and are located at the level of the RPE and choriocapillaris. Multiple active lesions may occur at any one time.
Multifocal choroiditis and panuveitis. Multiple, discreet lesions appearing in the early stage of the disease.
During the late stage of the disease, seen in the image below, the spots may become atrophic, with a rim of hyperpigmentation. These can assume the classic punched-out appearance with bands of subretinal fibrosis at their margins.
Multifocal choroiditis and panuveitis. Late stage of disease manifesting atrophic, punched-out lesions.
During the acute phase, optic disc edema may occur, which later develops to peripapillary scarring assuming a characteristic "napkin ring" subretinal fibrosis13 . Periphlebitis is often present with resultant retinal vasculature narrowing14 . Cystoid macular edema is present in approximately 10-20% of patients, and the incidence of choroidal neovascular membrane formation varies from 25-40%12,15 .
Diagnostic imaging: fluorescein angiography
During the early stage, the active lesions exhibit blockage of the early fluorescence followed by late staining. A rim of hyperfluorescence may or may not be present around the lesions. With the late stage of the disease, the most predominant feature is that of RPE window defects corresponding to the areas of the lesions. (See the images below.)
Multifocal choroiditis and panuveitis. Fluorescein angiogram demonstrating punctate hyperfluorescence due to staining of the lesions.
Multifocal choroiditis and panuveitis. Fluorescein angiogram demonstrating late phase transmission hyperfluorescence of lesions.
Diagnostic imaging: indocyanine green angiography
Similar to findings on fluorescein angiography, early lesions of MCP are hypofluorescent on indocyanine green (ICG) angiography. In contrast, early lesions of POHS tend to be hyperfluorescent16,17,18 .
Electrophysiologic and psychophysical studies
The electroretinogram (ERG) is normal in approximately 50% of patients with MCP. However, a report by Jacobson and coworkers looking at ERG testing in patients with AZOOR, which included patients with MCP, revealed interocular asymmetry in all patients tested with full field ERGs2 . In addition, moderate abnormalities in the a-wave suggest that there is dysfunction at the level of the photoreceptor outer segment. Similar findings have been noted in MEWDS and AMN using both the a-wave and the early receptor potential recordings19,20 . Serial multifocal ERG (MERG) testing reveals a diffuse loss of function over the entire test field that is often permanent21 .
The EOG findings are abnormal in approximately 60% of patients studied. Visual field testing sometimes demonstrates increased blind spot size22 . Scotomata are associated with clinical retinal lesions. Visual field pattern abnormalities correlate well with ERG a-wave amplitude2 . In addition, large temporal field defects that do not correspond to clinical lesions have also been noted21 .
Etiology
The etiology of MCP remains unknown. Extensive systemic medical evaluations have not yet identified a single common cause for MCP. Unlike POHS, where 90% of patients exhibit positive reactions to the histoplasmin skin test, only 25% of patients with MCP exhibit positive reactions to this skin test23 . Positive treponemal serology is evident in up to 27% of patients with MCP, yet no modification of the disease with penicillin treatments has been achieved to date.
Radiologic investigations of patients with MCP have demonstrated hilar adenopathy in a small minority of patients (approximately 4%) along with pulmonary calcification (approximately 10%). In conjunction with this, approximately 20% of patients with MCP have a positive Mantoux test. Half of those patients, when treated with antituberculous medications, have a decrease in the ocular inflammation. Sarcoidosis has also been diagnosed in more than one third of patients with MCP.
Other infections that have been associated with MCP include herpes simplex, herpes zoster, Epstein-Barr virus, Lyme disease, Toxocara canis, and West Nile virus24,25,26,27,28 . Despite this, many investigators still believe that MCP results from an underlying autoimmune mechanism, possibly triggered by an infectious agent. Histopathologic studies of ocular specimens from patients with MCP have revealed a predominant B-lymphocyte and plasma cell infiltrate of the choroid and choriocapillaris29 . In addition, a deposition of compliment and immunoglobulins at or above the Bruch membrane has been noted. A proliferation occurs of the pigment epithelium with hyperplastic changes and migration into the neurosensory retina29 .
Disease course and prognosis
Unfortunately, recurrence is very high in MCP, and the visual prognosis remains poor30,31,32 . Peripapillary atrophy with progressive subretinal fibrosis results in enlargement of a blind spot in approximately 43% of patients22,33 . Unlike the aforementioned conditions, the major cause of central visual loss is due to subretinal neovascular membrane formation (approximately 45%) and is not due to cystoid macular edema (approximately 13%)34 . Rarely, MCP may lead to serous retinal detachments. Approximately one third of patients with MCP maintain their initial visual acuity at onset, while another one third lose, on average, at least 2 or more Snellen lines30 .
Treatment
Treatment of MCP remains problematic. In a few cases, a prompt response occurs in the acute phase to high systemic corticosteroids with subsequent improvement in visual acuity. However, with each recurrence of the disease, a progressive diminution in the effect of corticosteroid treatment occurs.
Immunomodulatory therapy, using azathioprine, cyclosporine, or methotrexate, has often resulted in good control of the inflammation and in subsequent preservation of vision35 . In some instances, amelioration of the subretinal neovascular membrane has been noted with corticosteroid therapy32 . Specific laser therapies, both conventional laser therapy and photodynamic therapy (PDT), have been used with moderate success in managing subretinal neovascular membranes36,37,38 . Surgical treatment of subretinal neovascular membranes involving limited macular translocation has also been reported39 .
Diffuse subretinal fibrosis syndrome
This very rare and incompletely characterized entity was first described in 198240 . Many investigators have long suspected that diffuse subretinal fibrosis syndrome (DSFS) represents a variation of MCP. As well, this condition shares many features of punctate inner choroidopathy and other similar diseases in the AZOOR group41 . DSFS typically affects otherwise healthy individuals in their second decade (average age, approximately 20 y; range, 14-34 y). The condition is often bilateral. The association with axial myopia is questionable.
Signs and symptoms
Patients typically present with central visual loss and complaints of metamorphopsia. Clinical examination during the acute phase reveals multiple, small, yellow stellate lesions scattered throughout the posterior pole. Mild vitritis may be present with isolated pockets of subretinal fluid. In the chronic phase, the lesions become discrete with sharply angulated subretinal scar formation, as in the image below. In the macula, the lesions tend to coalesce, forming broad zones of subretinal fibrosis. Later complications can include serous and hemorrhagic macular detachment.
Diffuse subretinal fibrosis syndrome. This patient's right eye shows the typical subretinal angulated scar formation.
Diagnostic imaging: fluorescein angiography
As mentioned earlier, this condition shares many clinical features with that of MCP. This is also reflected in the fluorescein angiogram. The distinct features of DSFS on angiography are an early phase hypofluorescence in the areas of subretinal fluid loculation. During the late phase of the angiogram, extensive leakage (seen in the images below) is present at these sites that, in some cases, may suggest subretinal neovascularization40 .
Diffuse subretinal fibrosis syndrome. Midphase of fluorescein angiogram demonstrating progressive leakage hyperfluorescence.
Diffuse subretinal fibrosis syndrome. Late phase of the fluorescein angiogram demonstrating progressive leakage as hyperfluorescence.
Electrophysiologic and psychophysical studies
The findings on the ERG and the EOG are notoriously variable in this condition, with surprisingly intact studies in individuals with both acute and chronic involvement. Visual field testing reveals constriction peripherally with central scotomata that often correlate with the clinical lesions.
Etiology
As with MFC, no systemic associations with DSFS exist. Earlier suggestions that this condition may be due to as yet unknown hormonal irregularities in young women has not developed into any trend of significance42 . In view of the clinical and angiographic findings, this condition's clinical appearance is likely secondary to a primary RPE hyperplastic process43 .
Histologic evidence of immunoglobulin and complement deposition on the internal side of the Bruch membrane also suggests a focal inflammation of the RPE29 .
Disease course and prognosis
This condition is characterized by recurrent episodes with the fellow eye becoming involved within a 6-month period.
Treatment
Management of DSFS involves the use of corticosteroids early in the disease41 . This treatment is useful in sparing visual loss largely in the contralateral eye. Cyclosporin may be useful in those cases where steroid has failed to control the disease.
Punctate inner choroidopathy
First described by Watzke and associates in 1984, punctate inner choroidopathy (PIC) typically affects young, moderately myopic women who present with typical signs of ocular histoplasmosis but have negative serology or skin test for histoplasmosis32,44 . This rare condition is also one of the entities grouped under AZOOR45 . Other terms used to describe this condition include multifocal inner choroiditis and pseudohistoplasmosis. The average age of patients with PIC is 27 years with a range of 16-40 years. Females represent 90% of the patients with PIC and usually have bilateral ocular involvement46 .
Signs and symptoms
Patients present with blurred vision, photopsia, and central and peripheral scotomata; however, no history exists of any viral prodrome. PIC differs from POHS because patients with the latter tend to be more asymptomatic with regard to scotomata. Chronic chorioretinal scars also tend to be more stable in POHS than in PIC.
The initial visual acuity at presentation varies from 20/50 to 20/400. No anterior segment or external ocular signs of inflammation is evident. The characteristic lesion of PIC is essentially identical to that seen in ocular histoplasmosis with multiple (approximately 2-6) yellow-white spots (100-300 µm) of the inner choroid and retina largely confined to the posterior pole (see the image below). These lesions tend to assume a linear branching pattern. During the late stage of the disease, the spots become atrophic and pigmented.
Punctate inner choroidopathy. Pigmented central lesions in association with peripapillary scarring.
The classic triad of punched-out peripheral lesions in association with peripapillary atrophic scar formation and disciform macular scar seen in POHS is often present in patients with PIC. Small serous retinal detachments may form; however, they resolve spontaneously and usually require no treatment. Both optic disc edema and the presence of vitreous cells appear to be a variable finding in patients with PIC. The occurrence of subretinal neovascular membranes in this condition is 25-40%.
Diagnostic imaging: fluorescein angiography
Again, paralleling the findings in ocular histoplasmosis, the early phase of the angiogram demonstrates hyperfluorescence of the lesions, and the late phase (seen in the image below) is marked by leakage at the lesions.
Punctate inner choroidopathy. Late phase fluorescein angiogram of same patient as in Image 9 demonstrating halo hyperfluorescence of both peripapillary and inferior macular scars, which are more chronic relative to the more active superior macular lesion demonstrating leakage hyperfluorescence.
Electrophysiologic and psychophysical studies
The ERG findings are occasionally subnormal in patients with PIC. The EOG demonstrates very mild abnormalities of the Arden ratio. Visual field testing demonstrates central and paracentral scotomas. An enlarged blind spot may or may not be present.
Etiology
PIC likely represents a variant of MFC. This condition may represent either an inflammatory or infectious thrombosis of the choriocapillary layer by as of yet an unidentified organism that behaves very similarly to histoplasmosis.
Disease course and prognosis
Recurrences are common in PIC, usually occurring within the first 3 months32 . Despite this, visual outcome is good with approximately 50-75% of eyes having vision better than 20/25, especially if uncomplicated with choroidal neovascular membrane formation.
Treatment
A variable response to systemic corticosteroids occurs depending on the stage of the disease47,48,49 . Both conventional laser therapy and PDT have been used for the management of subretinal neovascular membranes with increasing success50,51,52,53 .
Acute Posterior Multifocal Placoid Pigment Epitheliopathy
In 1968, Gass first described acute posterior multifocal placoid pigment epitheliopathy (APMPPE)54 . This condition typically afflicts young or middle-aged, otherwise healthy, adults (average age is 25 y; range is 7-57 y) who experience an acute loss of visual acuity in one or both eyes55,56 . Neither a racial nor gender predilection exists for this condition. A slight preponderance of bilateral involvement does exist. The condition tends to resolve after approximately 7-11 weeks with near normal return of visual function. Although the RPE changes remain visible, usually no other ocular or systemic disturbances are evident. The typical course of the disease suggests an underlying viral inflammatory disorder1,57 .
Signs and symptoms
Typically, a rapid reduction initially occurs in visual acuity with or without a history of a preceding flulike illness or respiratory infection, often treated with systemic antibiotics. Clinically, APMPPE presents as multiple, well-circumscribed, flat subretinal lesions at the level of the RPE and choriocapillaris. These lesions are approximately 0.125- to 1-disc diameter in size and may be confluent. These typically scatter in the midperiphery and the posterior pole. Initially, they appear cream colored or grayish white in color, as seen in the image below. There is minimal evidence of anterior segment inflammation, although vitreous cells are present in as many as 50% of the patients. This is likely the result of a mild periphlebitis with exudation. In addition to vascular inflammation, mild optic disc edema also is noted. Very rarely, the condition can result in retinal edema, retinal hemorrhage, and subretinal neovascular membrane formation with hemorrhage58 .
Acute posterior multifocal placoid pigment epitheliopathy. Lesions are typically creamy white and are scattered throughout the posterior pole. Courtesy of Everett Ai, MD, San Francisco, Calif.
Diagnostic imaging: fluorescein angiography
Initially the lesions demonstrate hyperautofluorescence with hypoautofluorescent margins59,60,61,62 . The initial phase of the angiogram sometimes demonstrates prolonged filling of the choroidal vasculature. An early hypofluorescence often is attributed to a combination of incomplete and irregular filling of the choriocapillaris in conjunction with a masking effect produced by the edematous, swollen RPE cells. This is followed in a late phase with evidence of leakage and staining at the lesion sites. (See the images below.)
Acute posterior multifocal placoid pigment epitheliopathy. The lesions here are more peripheral than those in the previous image.
Midphase of fluorescein angiogram of the same patient as in the image directly above, demonstrating typical leakage and staining of the lesions.
Diagnostic imaging: indocyanine green angiography
The typical pattern for active and inactive lesions consists of hypofluorescent areas up to the late phase, suggesting choriocapillaris nonperfusion63,64,65,66 .
Diagnostic imaging: optical coherence tomography (OCT) scanning
Initially, the active phase of the disease demonstrates an anterior displacement and hyperreflectivity of neuroretina and outer reflective bands in areas overlying affected RPE.
With resolution, there is an accompanying regression of the prior displacement, increased reflectance of the outer reflective band, and mild disruption of the outer retinal layers. Quiescent lesions display a nodular, hyperreflective lesion on the plane of the RPE, with mild underlying backscattering from the choroidal layer, consistent with RPE atrophy.60,62,67,68,69
Electrophysiologic and psychophysical studies
Most patients with APMPPE have normal EOG findings. However, some patients may have diminished, subnormal EOG findings during the acute phase of the disease. Some may exhibit subnormal cone and rod ERGs. Permanent scotomata on visual field testing often are present that may or may not be coincident with the observable clinical lesions.
Etiology
Deutman and Van Buskirk believed that APMPPE represents a primary obstruction of the choroidal circulation with secondary RPE degeneration70,71 . This view is supported by ICG angiographic and OCT scan evidence63,64,65,66,62,67 . However, others, especially Gass, believe this to be a primary disease of the RPE1,54 . In view of this condition's association with a viral flulike illness, it is possible that an immune reaction to shared viral and RPE antigens with or without modification by the use of antibiotics might be underlying any primary RPE involvement. APMPPE, of all the conditions described in this article, has the greatest variety of associations with other systemic conditions61,72,73,74,75,76,77,78,79,80,81 , as follows:
- Thyroiditis
- Platelet aggregation abnormalities
- Lymphadenopathy
- Renal cell carcinoma
- Systemic mycobacterial infections
- Hepatomegaly
- Erythema nodosum
- Regional enteritis
- Cerebrovasculitis
- Vitamin B-12 deficiency
- Homocysteinemia
- Sarcoidosis
- Lyme disease
- Microvascular nephropathy
- Hemophagocytic syndrome
- Dysacusis
- Adenovirus type V
- Reaction to Swine Flu Vaccine
- Spinal fluid pleocytosis and elevated cerebral spinal fluid (CSF) protein
Disease course and prognosis
Fortunately, the prognosis for visual recovery is good, and many patients (>80%) experience better than 20/30 vision82 . Over a 2- to 6-week period, the lesions begin to fade, leaving atrophic, geographic-shaped lesions at the level of the RPE. Improvement in visual acuity often lags the resolution of the RPE lesions, which can take from weeks to months. Recurrences, unlike other conditions in these syndromes, are rare and usually occur within the first 6 months83 . If there is initial unilateral presentation, the second eye often lags from the first eye within a few days or weeks. A variant of APMPPE occurring in older patients and complicated by subsequent geographic atrophy and choroidal neovascular membrane formation has been described84 .
Treatment
Treatment of the acute phase of APMPPE with corticosteroids has shown limited benefits. Sub-Tenon and intravitreal triamcinolone have been used for associated complications, such as macular edema and choroidal neovascularization85,86 . Sporadic treatments with antituberculous and systemic antibiotics have also been reported but have not, as of yet, been proven to be effective87 . Photodynamic laser therapy has also been used to manage choroidal neovascularization in this condition85 .
Acute Retinal Pigment Epithelitis (Krill Disease)
This extremely rare condition was first described by Krill and Deutman in 197288 . Acute retinal pigment epithelitis (ARPE) is a self-limited RPE disease that typically occurs in young, otherwise healthy adults. It has a median age of onset of approximately 45 years, with a range of 16-75 years. A preponderance of involvement is evident in males (approximately two thirds). No racial predilection exists, and the condition is bilateral in approximately 40% of patients.
Signs and symptoms
Approximately one half of patients are asymptomatic at the time of presentation, with other patients describing a sudden decrease in vision with or without central scotomata and metamorphopsia. Unlike APMPPE, many patients (approximately 75%) have visual acuities around 20/30. The lesions appear dark gray to black in color with a yellow-white halo and are typically between 50-100 µm in size. Often, 1-4 golden-colored spots are arranged in discrete clusters around the macula. With resolution, the spots may either darken or lighten, but the halos remain. Extramacular lesions are rare, and, with time, a pattern of RPE migration may develop at the sites of the spots. Very rarely, this condition can result in macular edema or vitritis89,90 . (See the image below.)
Acute retinal pigment epitheliitis.
Diagnostic imaging: fluorescein angiography
During the active phase of the disease, hyperfluorescence is present in the center of the spots with normal halos. With time, the center of the spots may either remain hyperfluorescent or become hypofluorescent, while the halos might demonstrate hyperfluorescence, which is largely due to window defect pattern rather than any leakage91 .
Late phase fluorescein angiogram in a patient with acute retinal pigment epitheliitis displaying transmission hyperfluorescence.
Diagnostic imaging: optical coherence tomography scanning
Limited OCT scanning studies have demonstrated an abnormal foveal hyperreflectivity involving the outer nuclear layer and photoreceptors, with variable disruption of the retinal pigment epithelium73 .
Electrophysiologic and psychophysical studies
On Amsler grid testing, these patients sometimes describe variable central scotomas90 . Mild color vision abnormalities also have been described with this condition. EOG testing has yielded various results, from essentially normal to subnormal depending on the extent of RPE involvement in the macula. With resolution of the disease, there is a high rate of conversion back to normal in all tests.
Etiology
To date, systemic investigations of patients with this rare condition have failed to yield any conclusive viral etiology, although that clearly is suspected in this condition. Associations with rubella, Borrelia burgdorferi (Lyme disease), influenza, and hepatitis C infections have been made12,92,93,94 . Interestingly, in some instances this condition is believed to be a harbinger of central serous retinal choroidopathy (CSR)95 . A case of ARPE has been reported with the administration of intravenous bisphosphonate96 .
Disease course and prognosis
ARPE has a self-limited course, usually with complete resolution over a 6- to 12-week period97 . Fortunately, recurrences are rare98 .
Treatment
Currently, no therapeutic modalities are available that are recommended specifically for this condition.
Multiple Evanescent White Dot Syndrome
First described in 1984, MEWDS is a self-limited condition that afflicts otherwise healthy, young patients, usually in their second decade (average age is 28 y; range is 14-57 y), although cases involving children and elderly patients have been described99,100 . MEWDS shares many clinical and electrophysiologic features with AIBES and other entities in the AZOOR group4,7 . Despite that commonality, MEWDS is believed to be uniquely distinguishable, warranting its own separate identification10,101 . The condition usually presents unilaterally with few instances of later contralateral ocular involvement102 . There is a preponderance of the condition in women (approximately 75% of patients) and patients who are highly myopic103 . No racial predilection exists.
Signs and symptoms
In addition to presenting with blurred vision and multiple paracentral scotomata, patients also have symptoms of flulike illness (approximately 25-50%). Initial visual acuities on presentation vary from 20/25 to 20/300 (average 20/100). Vitreous cells are noted in approximately 50% of patients, despite the absence of any anterior segment or external ocular signs of inflammation.
The characteristic lesions in MEWDS consist of multiple, small (approximately 100-200 µm in diameter), gray-white patches, with each patch being made up of smaller white to light orange dots. These lesions appear to be at the level of the RPE and outer retina and typically are distributed in the perifoveal and peripapillary regions with rare involvement of the fovea itself. (See the image below.)
Multiple evanescent white dot syndrome. Acute manifestation of deep, white spots scattered throughout the posterior pole.
Peripapillary involvement with corresponding blind spot enlargement often can mimic the appearance of POHS104,105,106 . In the periphery, the dots become sparse and assume a somewhat radial pattern, in some instances paralleling the retinal vasculature. Later, the macula often exhibits a fine, granular, white- or orange-speckled appearance, as demonstrated in the image below107,108 . These specks are much smaller than the white dots and often are associated with an irregular light reflex of the internal limiting membrane.
Multiple evanescent white dot syndrome. This patient has spots similar to those seen in the patient in the previous image, but this patient also displays the almost pathognomonic granular changes in the macula.
Other posterior pole findings include splinter hemorrhages, venous sheathing, panuveitis, hyperemia or edema of the optic nerve head, and, very rarely, subretinal neovascular membrane109,110,111 .
Diagnostic Imaging: fluorescein angiography
Fundus autofluorescence is often present centrally, corresponding to the hypofluorescent lesions seen in ICG angiography112,107 . In the early phase of the fluorescein angiogram, there is a punctate hyperfluorescence of the gray-white patches that often display a wreath-shaped pattern. Leakage of dye at the optic disc is present in approximately 60% of patients. During the late phase of the angiogram, represented in the image below, a patchy, mottled pattern of hyperfluorescence is observed throughout the posterior pole, with staining of the optic nerve head. With resolution of the acute episode, the angiographic findings become much less prominent; but usually, subtle RPE window defects persist113 .
Multiple evanescent white dot syndrome. Fluorescein angiogram of the same patient as in the image directly previous to this one, demonstrating the characteristic late phase mottled hyperfluorescence and staining of the optic disc.
Diagnostic imaging: indocyanine green angiography
ICG angiography studies have demonstrated multiple deep, small, round, hypofluorescent choroidal lesions appearing early and persisting into the late phases114 of the disease. In some instances, the late phase hypofluorescence can appear as a series of small dots overlying larger spots. Many more lesions usually are observed on ICG angiography than are visible by clinical examination or fluorescein angiography115,116,117 . The hypofluorescent lesions in the ICG angiogram persist for a longer time than do those lesions displayed during fluorescein angiography118,119 . The ICG-defined lesions also closely correlate with visual function16 . ICG angiography in MEWDS can be helpful in establishing the diagnosis in cases with subtle clinical findings and also provide some useful guidance for therapy120,113 .
Diagnostic imaging: optical coherence tomography scanning
OCT scanning performed during the acute phase of MEWDS demonstrates a transient disruption of the foveal photoreceptor outer segments and the inner segment–outer segment (IS/OS) junction.121,122,123 )124 Line scans obtained through active white spot lesions show a dome-shaped, hyperreflective region in the subretinal space, with increased hyperreflectivity in the underlying choroidal space. With resolution of the spots, the OCT scan abnormalities gradually reverse.125 OCT scans obtained through the enlarged blind spot region show thinning of the outer nuclear layer in addition to IS/OS junction defects.101,113,123
Electrophysiologic and psychophysical studies
Despite clinical evidence of prominent RPE involvement in MEWDS, there is surprisingly only a brief manifestation of RPE dysfunction on electrophysiologic testing throughout most of the disease course. ERG performed during the acute phase demonstrates marked reduction in a-wave and early receptor potential (ERP) amplitudes, suggesting not only photoreceptor malfunction but also abnormal visual pigment regeneration kinetics.19,126 Selective cone ERG testing demonstrates predominantly more impairment of the S-cone system than of the L- and M-cone systems in the acute stage of MEWDS.127
Likewise, multifocal ERG testing has demonstrated not only reduction of amplitudes in areas corresponding to clinically visible lesions but also in the remainder of normal-appearing retina.21,128,129 The reduced amplitudes on multifocal ERG testing persist for many months after normalization of both the fundus appearance and the psychophysical tests.124,130
EOG testing demonstrates only mild abnormalities of the Arden ratio, again suggesting that abnormalities in MEWDS occur mainly at the level of the photoreceptors and the cycling of visual pigments.
Visual field testing demonstrates not only paracentral and central scotomas but also enlarged blind spots101,131,132 . Similarly, mapping regions of retinal sensitivity using microperimetry during the active phase of the condition demonstrates an enlarged blind spot.133 Visual evoked potentials (VEP) have demonstrated prolongation of the P100 latency persisting for many months after resolution of symptoms, suggesting more significant optic nerve involvement than previously known134 .
Etiology
The etiology of MEWDS remains unknown. The possibility of a viral cause has been considered in view of the elicitation of a history of a flulike illness in a significant proportion of patients. MEWDS has been associated with hepatitis A and B vaccine, as well as with yellow fever vaccine, further suggesting either a direct viral role or indirect viral antigen–induced response in the disease135,136,137,138 .
The high prevalence of MEWDS in female patients also suggests that hormonal factors may play a role in this condition. Despite a report of increased serum immunoglobulins (IgM and IgG) in MEWDS, workups for systemic disease in MEWDS are usually negative139 . However, an association between human leukocyte antigen B51 (HLA-B51) and MEWDS has been previously reported, possibly implicating a genetic predisposition for this disease140 .
As has been suggested, MEWDS might also share a similar etiology with multifocal choroiditis.141 In addition, cases of primary intraocular lymphoma and sympathetic ophthalmia have been described as presenting with an MEWDS type appearance.142,143,144 This is important in differentiating true etiologic factors from conditions that mimic MEWDS.
Disease course and prognosis
The disease usually has a self-limited course with good visual recovery, typically occurring within a 2-month period from the onset of symptoms (varies 2-16 wk). Approximately 90% of patients have better than 20/30 final visual acuity. Although late recurrences occasionally may occur, MEWDS is characterized by recovery of visual function and normalization of ERG findings145 . There is a return of normal peripheral funduscopic appearance, although macular changes may persist. Long-term follow-up of patients is critical, because in rare cases they can develop choroidal neovascularization.146,147
Treatment
In general, due to its self-limited course, no treatment for MEWDS currently is indicated. Systemic therapy with cyclosporine and corticosteroids have been described for isolated cases, with moderately good results.148,149 The use of photodynamic lasers and of the antivascular endothelial growth factor (antiVEGF) agent ranibizumab has been effective in treating MEWDS cases complicated by choroidal neovascularization.150,151
Birdshot (Vitiliginous) Retinochoroidopathy
Franceschetti and Babel may have incompletely described this chronic condition as early as 1949152 . First named by Ryan and Maumenee in 1980 to describe a rare, acquired, bilateral intraocular inflammatory disease, the condition also has been called vitiliginous chorioretinitis partly because of its fundus appearance and its loose association with cutaneous vitiligo in earlier reports153 . It typically involves middle- to late-aged patients (average age is approximately 52 y; range is 23-70 y). The disease primarily affects Caucasians, and, in the older age groups, especially beyond the fourth decade, females outnumber males.
Signs and symptoms
Patients typically present with not only decreased visual acuity but also symptoms of nyctalopia and dyschromatopsia. Rarely, patients may complain of photophobia and a reduction in visual field. The condition is painless. On clinical examination, minimal to no anterior segment inflammation is present. Visual acuities may vary at onset from 20/20 to 20/800, with most patients having a visual acuity of approximately 20/50.
The characteristic appearance of lesions in birdshot consists of multifocal patches of RPE and choroidal depigmentation seen below. Unlike other conditions in these syndromes, a halo of hyperpigmentation is absent within or at their margins. Individual lesions are typically 0.25-disc diameter in size and have certain uniformity in appearance. They can be cream colored or depigmented and round to oval in appearance and typically do not have a well-defined border. Hyperpigmentation may occur in some lesions in the late stages of the disease.
Birdshot (vitiliginous) retinochoroidopathy. Multiple, uniformly hypopigmented lesions with mild disc swelling.
The lesions typically are scattered throughout the postequatorial fundus in 1 of 4 patterns: (1) diffuse, (2) macular sparing, (3) macular predominance, and (4) asymmetrical154 . Often, the pattern is analogous to the splattering of birdshot from a shotgun. Initial foveal sparing is present. Birdshot can be associated with other retinal and ocular abnormalities, as follows155,156 :
- Cystoid macular edema
- Retinovascular attenuation
- Retinovascular sheathing
- Retinal and vitreous hemorrhages
- Epiretinal membrane formation
- Glaucoma optic atrophy
- Rhegmatogenous retinal detachment
- Subretinal neovascularization
- Optic disc edema (very rare)
- Retinal neovascularization (very rare)
- Serous macular degeneration (very rare)
Diagnostic imaging: fluorescein angiography
The key fluorescein angiographic findings in birdshot result from vascular leakage. This is quite pronounced in the perifoveal region with resultant cystoid macular edema. Acutely, the patches in birdshot are surprisingly silent, showing no abnormality. With time and enlargement of the patches, the individual lesions behave as window defects transmitting underlying fluorescence from the choroid.
In the early phase of the angiogram, there is a delay in retinal arteriole filling and circulation time, although retinal capillary nonperfusion typically is not seen with this disease. During this phase, the lesions are either not evident or are hypofluorescent. Choroidal vessels are often visible through the hypofluorescent lesions. With the late phase, the patches become hyperfluorescent, as demonstrated in the image below, with staining of the larger retinal veins and pooling, particularly in the setting of cystoid macular edema. Prolonged retinal circulation time has been noted in birdshot157 .
Birdshot (vitiliginous) retinochoroidopathy. Late phase fluorescein angiogram that demonstrates patchy hyperfluorescence.
Diagnostic imaging: indocyanine green angiography
In general, ICG angiography reveals a greater number of lesions than is evident either funduscopically or on fluorescein angiography154 . During the active phase of the disease, well-demarcated, hypofluorescent, round to oval spots appear throughout the posterior pole with relative sparing of the macula63 . These spots appear early during the arteriovenous phase and persist, unchanged during the late phase of the angiogram.
Progressive diffuse background fluorescence often occurs in the late phase of the angiogram in active disease. In the chronic or burned-out phase of the disease, ICG angiography reveals persistence of the characteristic hypofluorescent spots with absence of diffuse late phase hyperfluorescence158 . Remarkably, the ICG lesions are preserved despite an improvement in clinical appearance of the fundus lesions.
Electrophysiologic and psychophysical studies
The ERG in birdshot typically displays moderate-to-severe abnormalities of both rod and cone function (less than or equal to 80% of patients). A disproportionate decrease occurs in the amplitude of the b-wave compared with the a-wave (as demonstrated in the image below), and some believe that this decrease is the distinguishing feature of the disease159 .
Birdshot retinochoroidopathy electroretinogram response to a scotopic white light stimulus (arrow). Tracing demonstrates a slight disproportionate reduction of the b-wave response in comparison to the a-wave.
The EOG findings may be either normal or slightly subnormal (70% of patients), and, similarly, dark adaptation studies may show subnormal rod function. Patients also may exhibit nonspecific color vision defects. The visual field demonstrates a generalized constriction of peripheral fields with central scotomas or enlarged blind spots. These scotomas do not correspond clinically to the birdshot lesion distribution. Serial automated visual field testing has been found to be useful in the monitoring of the response to therapy160 .
Etiology
Birdshot is believed to result from a pathologic process occurring not only in the receptor-RPE-choroid complex but also a pathologic process occurring more diffusely throughout the neural layers of the retina. A genetic predisposition has been suggested since the incidence of the human leukocyte antigen A29 (HLA-A29) marker is present in approximately 85% of patients with birdshot retinochoroidopathy. This incidence rate is to be contrasted with 7% prevalence in the normal population161 . The HLA-A29.2 subtype is the most predominant in Caucasian patients with the disease154 .
An autoimmune mechanism as the cause of birdshot is supported by several findings. First, in vitro studies demonstrating lymphocyte-mediated immune responses to retinal S-antigen are present in most patients tested162,161 . Second, histologic examination reveals a cell-mediated inflammatory response to the outer retina and focal depigmentation of the choroidal melanocytes154 . Birdshot also has been associated with cutaneous vitiligo, elevated C4 complement, and elevated soluble interleukin 2 (IL-2) receptors163 . Therefore, a sort of altered immune mechanism likely is responsible for the clinical findings of this disease.
Disease course and prognosis
Birdshot, unlike the aforementioned conditions, is a fairly chronic disease with slow progression. It can be active for 3-4 years before finally going into remission162 . Birdshot is characterized by exacerbations and remissions. Although 73% of eyes have a visual acuity better than 20/60, ultimately, one third of patients have a final visual acuity of less than 20/200. Not surprisingly, the most significant cause of central visual loss in patients with birdshot is the presence of cystoid macular edema (40-60% of patients)154 . Rarely, the condition can resemble advanced tapetoretinal degeneration, particularly if left untreated164,165 .
Treatment
Currently, no single therapy has proven effective for treating patients with this condition. Various nonsteroidal anti-inflammatory drugs, immunosuppressives, and corticosteroids, in addition to antibiotics, have been tried with limited efficacy. Corticosteroid therapy in both local and systemic forms often is tried initially for moderate disease. Good control sometimes can be achieved with an initial induction followed by a slow taper to a maintenance dose166 . In situations where recurrence and exacerbation of the disease is present, a combination of azathioprine and prednisone may be effective in reducing the relapse rate167 .
Cyclosporine has been demonstrated to have an ameliorating effect on birdshot, both as a single agent and in combination with prednisone154 . Reports using a combination of ketoconazole and cyclosporine therapy have shown it to be effective not only in controlling the disease but also achieving stability with much lower doses of cyclosporine than conventionally used168,169 .
Another interesting treatment that has been reported for use in this condition is intravenous polyclonal immunoglobulin (IVIG). This treatment was effective in achieving significant remission without the use of corticosteroids or cytotoxic agents170 .
Serpiginous (Geographic) Choroiditis
Serpiginous or geographic helicoid peripapillary choroidopathy is a rare, progressive choroiditis that manifests a characteristic snakelike or propellerlike pattern of RPE and choriocapillaris atrophy. This condition was first described in 1932 by Junius, but it was not until 1974 that Shatz, Maumenee, and Patz characterized the condition;171,172 Hamilton and Bird also described this condition in the same year173 .
The disease typically affects otherwise healthy patients in their fourth to sixth decades. This condition is more prevalent in Caucasians, and no gender predilection exists. The condition may present initially as unilateral; however, with time, eventually all cases become bilateral. The interval between the primary and contralateral eye involvement may be several years.
Signs and symptoms
Patients typically complain of blurred vision in association with metamorphopsia and scotomas, mostly central or paracentral. Clinical examination during the acute phase reveals an initial visual acuity of approximately 20/40 (range 20/20 to counting fingers; dependent on extent of foveal involvement). Although occasional nongranulomatous uveitis may be present, both anterior segment and external ocular examinations are usually unremarkable174 . Vitritis may be present in 25-30% of patients.
The characteristic lesion in serpiginous choroiditis is a yellow to gray geographic pattern, usually with well-defined borders. The lesion typically arises from the peripapillary region and spreads centrifugally in a geographic-like or, as in the image below, pseudopod-like fashion. Although rare, cases have been reported in which the macula initially is affected175,176 . Regions of quiescent atrophy are present in the wake of the advancing, active border of the lesion. Isolated, noncontiguous areas of activity may be present. With time, pigment clumping and hypopigmentation of the RPE occur, with clear visibility of the underlying large choroidal vessels within these atrophic patches177 . Despite bilateral involvement, a high degree of asymmetry between both eyes often is present.
Serpiginous (geographic) choroiditis. This patient shows an old, inactive serpiginous scar extending in a pseudopod-like fashion from the optic disc. Courtesy of Patrick Monahan, MD, San Jose, Calif.
Unfortunately, this condition has a predilection for the temporal rather than the nasal fundus. Although the overlying retina is usually edematous and may progress to serous detachment, the retinal vessels and the optic nerve head usually appear normal throughout the disease. Choroidal neovascularization develops in approximately 25% of patients178,179 . Other rare associations with serpiginous choroiditis include retinal periphlebitis, retinal and disc neovascularization, branch retinal vein occlusion, and RPE detachment176,180,181 .
Diagnostic imaging: fluorescein angiography
Angiographic appearance of serpiginous choroiditis varies according to the state of the disease. The lesions in the acute phase of the disease demonstrate blockage of fluorescence during the early transit phase of the angiogram. Eventually, staining occurs during the late phases. The hypofluorescence during the acute phase is attributed to a combination of both RPE cell edema and choriocapillaris nonperfusion. Staining of the vein walls may be demonstrated when focal areas of retinal phlebitis are present.
The inactive phase is characterized by a patchy diminution of the early choroidal flush due to the destruction of the choriocapillaris. There is unmasking of the underlying choroidal vessel fluorescence, this occurring in areas of healed lesions, which become atrophic scars. The staining at the margins of inactive lesions results from leakage of adjacent preserved choriocapillaris. (See the images below.)
Serpiginous (geographic) choroiditis. Chronic atrophic lesions that display widespread geographic chorioretinal atrophy with moderate foveal sparing.
Serpiginous (geographic) choroiditis. A transit-phase fluorescein angiogram of the same eye as in the above image demonstrates leakage and staining hyperfluorescence at the margins of the atrophic lesions. The underlying large choroidal vessels are seen easily within the atrophic lesions.
In the very late phases of the angiogram, diffuse hyperfluorescence of the lesions occurs due to staining of the sclera and fibrous tissues. The staining typically progresses from the peripheral margins toward the center, similar to that seen in APMPPE.
Electrophysiologic and psychophysical studies
The ERG amplitude and implicit time responses are abnormal in approximately 11% of patients with serpiginous. The EOG findings are likewise abnormal in 25% of patients. The degree of ERG and EOG abnormality is correlated closely with the extent of clinically involved retina176 . Visual field testing reveals absolute or relative scotomata also corresponding with clinical retinal lesions. Central, cecocentral, and paracentral scotomata are the predominant feature on visual field testing.
Etiology
The etiology of serpiginous choroiditis remains elusive, although it is known that the lesions appear to be at the level of the RPE and choriocapillaris. Histopathologic studies reveal that the disease is primarily a nongranulomatous choroiditis182 . The suggestion that serpiginous may be caused by immunologic mechanisms is strengthened by its association with the human leukocyte antigen A2 (HLA-A2) and human leukocyte antigen B7 (HLA-B7) histocompatibility and also by the occurrence of other inflammatory lesions in the involved eye180 . Evidence of serologic reaction to retinal S-antigen in affected patients lends further support to alterations in immune responsiveness175 . Other associations with serpiginous choroiditis include sarcoidosis, tuberculosis, extrapyramidal dystonia, and elevated factor VIII-von Willebrand factor176,183,184,185 .
Disease course and prognosis
The disease is characterized by an episodic and indolent course with recurrences often going undetected unless there is macular involvement. Reactivation of quiescent borders of single lesions can occur, and new activity may arise from independent foci in the peripheral fundus. Fibrous metaplasia of the RPE develops within the area of chorioretinal atrophy in approximately 50% of patients. This is particularly prominent nasally and in the peripapillary region. The prognosis for retaining good visual acuity is poor. Only 45% of patients are able to maintain normal visual acuity. The contralateral eye may be involved within months or several years following the initial process in the involved eye. Despite that, most patients are able to maintain good central and peripheral function in at least 1 eye.
Treatment
Most investigators agree that the efficacy of any therapeutic agent has not yet been established in serpiginous choroiditis. Laser photocoagulation treatment does not appear to slow the progression of this disease. Treatments using systemic corticosteroids, chlorambucil, and cyclosporine-A have had variable responses186,187 . Combination therapy with azathioprine, cyclosporine-A, and prednisone may hold promise188 .
Diffuse Unilateral Subacute Neuroretinitis
Diffuse unilateral subacute neuroretinitis (DUSN), which is caused by the chronic subretinal migration of 1 of at least 2 species of nematodes, characteristically involves children or young adults with a slight male preponderance among patients. Patients are otherwise healthy and are often asymptomatic at time of presentation.
Signs and symptoms
Patients often present quite late in the disease with typically poor visual acuities, usually less than 20/200. Those few cases that have presented during the acute period have demonstrated a moderate degree of vitritis with optic disc swelling and a variable anterior chamber reaction, with or without hypopyon.
The characteristic posterior pole findings are those of focal, gray-white or yellow-white spots developing in the deep layers of the retina and also at the level of the RPE. These normally develop within several days to weeks from the onset of symptoms. The lesions tend to cluster in the macula or juxtamacular region and typically last several days before fading. Occasionally, a subretinal worm (500-2000 µm length, 25 µm in width), such as that present in the eye below, can be seen.
Diffuse unilateral subacute neuroretinitis. Attempted focal laser photocoagulation of a subretinal nematode suspected of being Baylisascaris procyonis. Courtesy of Everett Ai, MD, San Francisco, Calif.
The worm was only later discovered to have migrated from the original site, which initially was targeted for laser treatment.
A second laser treatment was successful at destroying the worm.
The same eye immediately after the second laser treatment, showing not only the hypofluorescent laser-treated areas but also the characteristic mottled hyperfluorescence of diffuse retinal pigment epithelium and choriocapillaris destruction.
In the inactive phase, the posterior pole exhibits extensive mottling of the RPE, assuming a pseudo–retinitis pigmentosa appearance. There is also extensive retinovascular narrowing and sheathing with optic atrophy. Subretinal neovascularization may develop at this stage. A mild to moderate anterior chamber and vitreous cell reaction may be present even in the inactive stage. The patient often has an afferent pupillary defect.
Diagnostic imaging: fluorescein angiography
In the very early stage of the disease, angiogram findings may be entirely normal. If lesions are present, hypofluorescence of the lesions occurs during the early phase of the angiogram, and the lesions typically stain during the late phase. In addition, leakage occurs from the capillaries overlying the optic nerve, in addition to more diffuse perivenous leakage occurring in the retina. In a more typical late stage of the disease, an increase occurs in the background choroidal fluorescence due to extensive RPE dropout and loss of pigmentation. Hyperfluorescence, indicative of RPE atrophy, occurs in the periphery and the peripapillary regions, exhibiting fine, mottled hyperfluorescence, particularly in the macular region. (See the image below.) If a worm is present, it can be seen as a hypofluorescent lesion.
Diffuse unilateral subacute neuroretinitis. Late stage of the disease presenting the characteristic pseudo–retinitis pigmentosa features.
Electrophysiologic and psychophysical studies
Often, a moderate-to-severe reduction in the ERG occurs. With later stages of the disease, a disproportionate decrease occurs with the b-wave amplitude relative to the decrease in the a-wave amplitude. In rare instances, the ERG may be extinguished.
Etiology
Leading the list of suspected causative agents in this disease are the nematodes Toxocara canis (dog roundworm), Ancylostoma caninum (dog hookworm), and Baylisascaris procyonis (raccoon intestinal nematode)46,189 . Clinically, 2 types of worms apparently have been described with this condition. They are differentiated by length. Smaller worms (400-1000 µm) and longer worms (1500-2000 µm) may wander in the subretinal space for many years and cause progressive ocular damage. However, the nematode may be found during any stage of the disease.
The worm often is located in the deep, white retinal exudative lesions. Surgical removal of a subretinal nematode in a patient with DUSN identified the causative organism as a third stage T canis larva190 . Serologic testing for Toxocara is typically negative in patients with DUSN.
The damage caused by the organisms appears to involve a local toxic tissue reaction to the outer retina caused by the worm's byproducts, in addition to a more diffuse toxic reaction affecting both the inner and the outer retinal tissues that is believed to be due to the host's immunologic defenses. Eosinophilia infrequently is detected, and patients do not manifest evidence of systemic disease.
Histopathologic examination of the few eyes that have been examined with DUSN reveals a largely nongranulomatous vitritis, retinitis, and retinal and optic nerve perivasculitis. Low-grade, patchy, nongranulomatous choroiditis also is present. Extensive degeneration of the peripheral retina occurs, particularly of the posterior region within the arcades. Mild-to-moderate degenerative changes in the RPE also have been described. Not surprisingly, optic atrophy is a common feature of these eyes.
Disease course and prognosis
Following the acute phase of the disease, focal and more diffuse depigmentation of the RPE develops over the ensuing weeks or months. Pigment migration occurs into the overlying retina with a gradual narrowing of the retinal vasculature. Retinal hemorrhages may result from choroidal neovascularization and can result in occasional serous retinal detachments.
Treatment
Treatment of patients with DUSN has not yet been optimized to date. Three modalities of treatment, of which a combination usually is applied, are available. Argon laser photocoagulation is effective in destroying the worm and in causing minimal inflammatory reaction. Surgical (transvitreal) removal of a subretinal nematode elicits less inflammatory response but is accompanied with risks inherent to this treatment. The use of such medicinals as antihelminthics (eg, thiabendazole, diethylcarbamazine) or antifilarial agents (eg, Ivermectin) may be used as adjunctive treatment.
Conclusion
With the exception of DUSN, the idiopathic multifocal choroidopathy syndromes discussed remain problematic, not only from an etiologic point of view but also from a classification point of view. Although there is a practical benefit to combine these entities under one group, such as AZOOR or multifocal choroidopathy, sufficiently unique characteristics in each of these conditions still exist that make them distinct from each other. Additionally, many instances occur where the patient's symptomatology and clinical findings overlap between the entities. Similarly, although many findings point toward an infectious and/or immunologic mechanism as the cause of these conditions, no conclusive evidence for either one has yet been demonstrated. Until more clinical and histologic information regarding these entities is available, current attempts at grouping or subgrouping these conditions proves inadequate in the long run.
Multimedia
 | Media file 1: Multifocal choroiditis and panuveitis. Multiple, discreet lesions appearing in the early stage of the disease. |
 | Media file 2: Multifocal choroiditis and panuveitis. Fluorescein angiogram demonstrating punctate hyperfluorescence due to staining of the lesions. |
 | Media file 3: Multifocal choroiditis and panuveitis. Late stage of disease manifesting atrophic, punched-out lesions. |
 | Media file 4: Multifocal choroiditis and panuveitis. Fluorescein angiogram demonstrating late phase transmission hyperfluorescence of lesions. |
 | Media file 5: Diffuse subretinal fibrosis syndrome. This patient's right eye shows the typical subretinal angulated scar formation. |
 | Media file 6: Diffuse subretinal fibrosis syndrome. Midphase of fluorescein angiogram demonstrating progressive leakage hyperfluorescence. |
 | Media file 7: Diffuse subretinal fibrosis syndrome. Late phase of the fluorescein angiogram demonstrating progressive leakage as hyperfluorescence. |
 | Media file 8: Punctate inner choroidopathy. Pigmented central lesions in association with peripapillary scarring. |
 | Media file 9: Punctate inner choroidopathy. Pigmented peripheral lesions. |
 | Media file 10: Punctate inner choroidopathy. Late phase fluorescein angiogram of same patient as in Image 9 demonstrating halo hyperfluorescence of both peripapillary and inferior macular scars, which are more chronic relative to the more active superior macular lesion demonstrating leakage hyperfluorescence. |
 | Media file 11: Multiple evanescent white dot syndrome. Acute manifestation of deep, white spots scattered throughout the posterior pole. |
 | Media file 12: Multiple evanescent white dot syndrome. This patient has spots similar to those seen in the patient in the previous image, but this patient also displays the almost pathognomonic granular changes in the macula. |
 | Media file 13: Multiple evanescent white dot syndrome. Fluorescein angiogram of the same patient as in the image directly previous to this one, demonstrating the characteristic late phase mottled hyperfluorescence and staining of the optic disc. |
 | Media file 14: Acute posterior multifocal placoid pigment epitheliopathy. Lesions are typically creamy white and are scattered throughout the posterior pole. Courtesy of Everett Ai, MD, San Francisco, Calif. |
 | Media file 15: Acute posterior multifocal placoid pigment epitheliopathy. The lesions here are more peripheral than those in the previous image. |
 | Media file 16: Midphase of fluorescein angiogram of the same patient as in the image directly above, demonstrating typical leakage and staining of the lesions. |
 | Media file 17: Acute retinal pigment epitheliitis. |
 | Media file 18: Late phase fluorescein angiogram in a patient with acute retinal pigment epitheliitis displaying transmission hyperfluorescence. |
 | Media file 19: Serpiginous (geographic) choroiditis. This patient shows an old, inactive serpiginous scar extending in a pseudopod-like fashion from the optic disc. Courtesy of Patrick Monahan, MD, San Jose, Calif. |
 | Media file 20: Serpiginous (geographic) choroiditis. Chronic atrophic lesions that display widespread geographic chorioretinal atrophy with moderate foveal sparing. |
 | Media file 21: Serpiginous (geographic) choroiditis. A transit-phase fluorescein angiogram of the same eye as in the above image demonstrates leakage and staining hyperfluorescence at the margins of the atrophic lesions. The underlying large choroidal vessels are seen easily within the atrophic lesions. |
 | Media file 22: Birdshot (vitiliginous) retinochoroidopathy. Multiple, uniformly hypopigmented lesions with mild disc swelling. |
 | Media file 23: Birdshot (vitiliginous) retinochoroidopathy. Late phase fluorescein angiogram that demonstrates patchy hyperfluorescence. |
 | Media file 24: Birdshot retinochoroidopathy electroretinogram response to a scotopic white light stimulus (arrow). Tracing demonstrates a slight disproportionate reduction of the b-wave response in comparison to the a-wave. |
 | Media file 25: Diffuse unilateral subacute neuroretinitis. Attempted focal laser photocoagulation of a subretinal nematode suspected of being Baylisascaris procyonis. Courtesy of Everett Ai, MD, San Francisco, Calif. |
 | Media file 26: The worm was only later discovered to have migrated from the original site, which initially was targeted for laser treatment. |
 | Media file 27: A second laser treatment was successful at destroying the worm. |
 | Media file 28: The same eye immediately after the second laser treatment, showing not only the hypofluorescent laser-treated areas but also the characteristic mottled hyperfluorescence of diffuse retinal pigment epithelium and choriocapillaris destruction. |
 | Media file 29: Diffuse unilateral subacute neuroretinitis. Late stage of the disease presenting the characteristic pseudo–retinitis pigmentosa features. |
Keywords
multifocal choroidopathy syndromes, choroid, choroidal, choroiditis, panuveitis, choroidal neovascularization, retinal pigment epithelium, multifocal choroiditis, acute posterior multifocal placoid pigment epitheliopathy, acute retinal pigment epithelitis, Krill disease, multiple evanescent white dot syndrome, birdshot retinochoroidopathy, serpiginous choroiditis, diffuse unilateral subacute neuroretinitis
More on Multifocal Choroidopathy Syndromes |
| References |
| Further Reading |
References
Gass JD. Acute zonal occult outer retinopathy. Donders Lecture: The Netherlands Ophthalmological Society, Maastricht, Holland, June 19, 1992. J Clin Neuroophthalmol. Jun 1993;13(2):79-97. [Medline].
Jacobson SG, Morales DS, Sun XK, et al. Pattern of retinal dysfunction in acute zonal occult outer retinopathy. Ophthalmology. Aug 1995;102(8):1187-98. [Medline].
Francis PJ, Marinescu A, Fitzke FW, et al. Acute zonal occult outer retinopathy: towards a set of diagnostic criteria. Br J Ophthalmol. Jan 2005;89(1):70-3. [Medline].
Volpe NJ, Rizzo JF, Lessell S. Acute idiopathic blind spot enlargement syndrome: a review of 27 new cases. Arch Ophthalmol. Jan 2001;119(1):59-63. [Medline].
Machida S, Haga-Sano M, Ishibe T, et al. Decrease of blue cone sensitivity in acute idiopathic blind spot enlargement syndrome. Am J Ophthalmol. Aug 2004;138(2):296-9. [Medline].
Watzke RC, Shults WT. Clinical features and natural history of the acute idiopathic enlarged blind spot syndrome. Ophthalmology. Jul 2002;109(7):1326-35. [Medline].
Gass JD. Overlap among acute idiopathic blind spot enlargement syndrome and other conditions. Arch Ophthalmol. Nov 2001;119(11):1729-31. [Medline].
Kondo N, Kondo M, Miyake Y. Acute idiopathic blind spot enlargement syndrome: prolonged retinal dysfunction revealed by multifocal electroretinogram technique. Am J Ophthalmol. Jul 2001;132(1):126-8. [Medline].
Turbeville SD, Cowan LD, Gass JD. Acute macular neuroretinopathy: a review of the literature. Surv Ophthalmol. Jan-Feb 2003;48(1):1-11. [Medline].
Jampol LM, Wiredu A. MEWDS, MFC, PIC, AMN, AIBSE, and AZOOR: one disease or many?. Retina. 1995;15(5):373-8. [Medline].
Nozik RA, Dorsch W. A new chorioretinopathy associated with anterior uveitis. Am J Ophthalmol. Nov 1973;76(5):758-62. [Medline].
Quillen DA, Davis JB, Gottlieb JL, et al. The white dot syndromes. Am J Ophthalmol. Mar 2004;137(3):538-50. [Medline].
Buerk BM, Rabb MF, Jampol LM. Peripapillary subretinal fibrosis: a characteristic finding of multifocal choroiditis and panuveitis. Retina. Feb-Mar 2005;25(2):228-9. [Medline].
Schenck F, Boke W. Retinal vasculitis with multifocal retinochoroiditis. Int Ophthalmol. Oct 1990;14(5-6):401-4. [Medline].
Krill AE, Archer D. Choroidal neovascularization in multifocal (presumed histoplasmin) choroiditis. Arch Ophthalmol. Nov 1970;84(5):595-604. [Medline].
Cimino L, Auer C, Herbort CP. Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies. Ocul Immunol Inflamm. Dec 2000;8(4):275-83. [Medline].
Parnell JR, Jampol LM, Yannuzzi LA, et al. Differentiation between presumed ocular histoplasmosis syndrome and multifocal choroiditis with panuveitis based on morphology of photographed fundus lesions and fluorescein angiography. Arch Ophthalmol. Feb 2001;119(2):208-12. [Medline].
Vadala M, Lodato G, Cillino S. Multifocal choroiditis: indocyanine green angiographic features. Ophthalmologica. Jan-Feb 2001;215(1):16-21. [Medline].
Sieving PA, Fishman GA, Jampol LM, Pugh D. Multiple evanescent white dot syndrome. II. Electrophysiology of the photoreceptors during retinal pigment epithelial disease. Arch Ophthalmol. May 1984;102(5):675-9. [Medline].
Sieving PA, Fishman GA, Salzano T, Rabb MF. Acute macular neuroretinopathy: early receptor potential change suggests photoreceptor pathology. Br J Ophthalmol. Apr 1984;68(4):229-34. [Medline].
Oh KT, Folk JC, Maturi RK, et al. Multifocal electroretinography in multifocal choroiditis and the multiple evanescent white dot syndrome. Retina. 2001;21(6):581-9. [Medline].
Khorram KD, Jampol LM, Rosenberg MA. Blind spot enlargement as a manifestation of multifocal choroiditis. Arch Ophthalmol. Oct 1991;109(10):1403-7. [Medline].
Dreyer RF, Gass DJ. Multifocal choroiditis and panuveitis. A syndrome that mimics ocular histoplasmosis. Arch Ophthalmol. Dec 1984;102(12):1776-84. [Medline].
Bloom SM, Snady-McCoy L. Multifocal choroiditis uveitis occurring after herpes zoster ophthalmicus. Am J Ophthalmol. Dec 15 1989;108(6):733-5. [Medline].
Bodine SR, Marino J, Camisa TJ, Salvate AJ. Multifocal choroiditis with evidence of Lyme disease. Ann Ophthalmol. May 1992;24(5):169-73. [Medline].
Frau E, Dussaix E, Offret H, Bloch-Michel E. The possible role of herpes viruses in multifocal choroiditis and panuveitis. Int Ophthalmol. Oct 1990;14(5-6):365-9. [Medline].
Spaide RF, Sugin S, Yannuzzi LA, DeRosa JT. Epstein-Barr virus antibodies in multifocal choroiditis and panuveitis. Am J Ophthalmol. Oct 15 1991;112(4):410-3. [Medline].
Tiedeman JS. Epstein-Barr viral antibodies in multifocal choroiditis and panuveitis. Am J Ophthalmol. May 15 1987;103(5):659-63. [Medline].
Palestine AG, Nussenblatt RB, Chan CC, et al. Histopathology of the subretinal fibrosis and uveitis syndrome. Ophthalmology. Jun 1985;92(6):838-44. [Medline].
Vianna RN, Ozdal PC, Filho JP, et al. Longterm follow-up of patients with multifocal choroiditis and panuveitis. Acta Ophthalmol Scand. Dec 2004;82(6):748-53. [Medline].
Joondeph BC, Tessler HH. Clinical course of multifocal choroiditis: photographic and angiographic evidence of disease recurrence. Ann Ophthalmol. Nov 1991;23(11):424-9. [Medline].
Morgan CM, Schatz H. Recurrent multifocal choroiditis. Ophthalmology. Sep 1986;93(9):1138-47. [Medline].
Reddy CV, Brown J, Folk JC, et al. Enlarged blind spots in chorioretinal inflammatory disorders. Ophthalmology. Apr 1996;103(4):606-17. [Medline].
Watzke RC, Claussen RW. The long-term course of multifocal choroiditis (presumed ocular histoplasmosis). Am J Ophthalmol. Jun 1981;91(6):750-60. [Medline].
Michel SS, Ekong A, Baltatzis S, Foster CS. Multifocal choroiditis and panuveitis: immunomodulatory therapy. Ophthalmology. Feb 2002;109(2):378-83. [Medline].
Coquelet P, Postelmans L, Snyers B, Verougstraete C. Successful photodynamic therapy combined with laser photocoagulation in three eyes with classic subfoveal choroidal neovascularisation affecting two patients with multifocal choroiditis: case reports. Bull Soc Belge Ophtalmol. 2002;69-73. [Medline].
Gebka A, Raczynska K, Ciechanowski C, Krajka-Lauer J. [Photodynamic therapy with verteporfin in treating the choroidal neovascularisation secondary to multifocal choroiditis]. Klin Oczna. 2005;107(1-3):118-20. [Medline].
Gerth C, Spital G, Lommatzsch A, et al. Photodynamic therapy for choroidal neovascularization in patients with multifocal choroiditis and panuveitis. Eur J Ophthalmol. Jan-Feb 2006;16(1):111-8. [Medline].
Fujii GY, Humayun MS, Pieramici DJ, et al. Initial experience of inferior limited macular translocation for subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration. Am J Ophthalmol. Jan 2001;131(1):90-100. [Medline].
Doran RM, Hamilton AM. Disciform macular degeneration in young adults. Trans Ophthalmol Soc U K. 1982;102 (Pt 4):471-80. [Medline].
Gandorfer A, Ulbig MW, Kampik A. Diffuse subretinal fibrosis syndrome. Retina. 2000;20(5):561-3. [Medline].
Salvador F, Garcia-Arumi J, Mateo C, et al. Multifocal choroiditis with progressive subretinal fibrosis. Report of two cases. Ophthalmologica. 1994;208(3):163-7. [Medline].
Cantrill HL, Folk JC. Multifocal choroiditis associated with progressive subretinal fibrosis. Am J Ophthalmol. Feb 15 1986;101(2):170-80. [Medline].
Watzke RC, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J Ophthalmol. Nov 1984;98(5):572-84. [Medline].
Taira K, Nakazawa M, Takano Y, Ota T. Acute zonal occult outer retinopathy in the fellow eye 5 years after presentation of punctate inner choroidopathy. Graefes Arch Clin Exp Ophthalmol. Nov 29 2005;1-3. [Medline].
Gass JD. Stereoscopic Atlas of Macular Diseases Diagnosis and Treatment. St Louis: Mosby-Year Book Inc;1987.
Brueggeman RM, Noffke AS, Jampol LM. Resolution of punctate inner choroidopathy lesions with oral prednisone therapy. Arch Ophthalmol. Jul 2002;120(7):996. [Medline].
Holekamp NM, Thomas MA, Pearson A. The safety profile of long-term, high-dose intraocular corticosteroid delivery. Am J Ophthalmol. Mar 2005;139(3):421-8. [Medline].
Levy J, Shneck M, Klemperer I, Lifshitz T. Punctate inner choroidopathy: resolution after oral steroid treatment and review of the literature. Can J Ophthalmol. Oct 2005;40(5):605-8. [Medline].
Chatterjee S, Gibson JM. Photodynamic therapy: a treatment option in choroidal neovascularisation secondary to punctate inner choroidopathy. Br J Ophthalmol. Jul 2003;87(7):925-7. [Medline].
Leslie T, Lois N, Christopoulou D. Photodynamic therapy for inflammatory choroidal neovascularisation unresponsive to immunosuppression. Br J Ophthalmol. Feb 2005;89(2):147-50. [Medline].
Lim JI, Flaxel CJ, LaBree L. Photodynamic therapy for choroidal neovascularisation secondary to inflammatory chorioretinal disease. Ann Acad Med Singapore. Mar 2006;35(3):198-202. [Medline].
Wachtlin J, Heimann H, Behme T, Foerster MH. Long-term results after photodynamic therapy with verteporfin for choroidal neovascularizations secondary to inflammatory chorioretinal diseases. Graefes Arch Clin Exp Ophthalmol. Nov 2003;241(11):899-906. [Medline].
Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. Aug 1968;80(2):177-85. [Medline].
Burés-Jelstrup A, Adán A, Casaroli-Marano R. [Acute posterior multifocal placoid pigment epitheliopathy. Study of 16 cases]. Arch Soc Esp Oftalmol. May 2007;82(5):291-7. [Medline].
Mensah E, Vafidis GC. Acute posterior multifocal placoid pigment epitheliopathy in a 7-year-old girl. J Pediatr Ophthalmol Strabismus. Jul-Aug 2002;39(4):239-41. [Medline].
Holt WS, Regan CD, Trempe C. Acute posterior multifocal placoid pigment epitheliopathy. Am J Ophthalmol. Apr 1976;81(4):403-12. [Medline].
Garg S, Jampol LM. Macular serous detachment in acute posterior multifocal placoid pigment epitheliopathy. Retina. Aug 2004;24(4):650-1. [Medline].
Spaide RF. Autofluorescence imaging of acute posterior multifocal placoid pigment epitheliopathy. Retina. Apr 2006;26(4):479-82. [Medline].
Souka AA, Hillenkamp J, Gora F, Gabel VP, Framme C. Correlation between optical coherence tomography and autofluorescence in acute posterior multifocal placoid pigment epitheliopathy. Graefes Arch Clin Exp Ophthalmol. Oct 2006;244(10):1219-23. [Medline].
Framme C, Sachs HG, Gabler B, Roider J. Fundus autofluorescence in APMPPE in association with lyme disease. Retina. Oct 2002;22(5):653-7. [Medline].
Batioglu F, Ozmert E, Kurt R. Fundus autofluorescence and spectral optical coherence tomography findings in a case with acute posterior multifocal placoid pigment epitheliopathy. Ann Ophthalmol (Skokie). Fall-Winter 2008;40(3-4):185-9. [Medline].
Howe LJ, Stanford MR, Graham EM, Marshall J. Choroidal abnormalities in birdshot chorioretinopathy: an indocyanine green angiography study. Eye. 1997;11 (Pt 4):554-9. [Medline].
Park D, Schatz H, McDonald HR, Johnson RN. Indocyanine green angiography of acute multifocal posterior placoid pigment epitheliopathy. Ophthalmology. Dec 1995;102(12):1877-83. [Medline].
Bouchenaki N, Cimino L, Auer C, Tao Tran V, Herbort CP. Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography. Klin Monatsbl Augenheilkd. Apr 2002;219(4):243-9. [Medline].
Schneider U, Inhoffen W, Gelisken F. Indocyanine green angiography in a case of unilateral recurrent posterior acute multifocal placoid pigment epitheliopathy. Acta Ophthalmol Scand. Feb 2003;81(1):72-5. [Medline].
Lim LL, Watzke RC, Lauer AK, Smith JR. Ocular coherence tomography in acute posterior multifocal placoid pigment epitheliopathy. Clin Experiment Ophthalmol. Nov 2006;34(8):810-2. [Medline].
Scheufele TA, Witkin AJ, Schocket LS, Rogers AH, Schuman JS, Ko TH. Photoreceptor atrophy in acute posterior multifocal placoid pigment epitheliopathy demonstrated by optical coherence tomography. Retina. Dec 2005;25(8):1109-12. [Medline].
Lofoco G, Ciucci F, Bardocci A, Quercioli P, Steigerwalt RD Jr, De Gaetano C. Optical coherence tomography findings in a case of acute multifocal posterior placoid pigment epitheliopathy (AMPPPE). Eur J Ophthalmol. Jan-Feb 2005;15(1):143-7. [Medline].
Deutman AF, Oosterhuis JA, Boen-Tan TN, Aan de Kerk AL. Acute posterior multifocal placoid pigment epitheliopathy. Pigment epitheliopathy of choriocapillaritis?. Br J Ophthalmol. Dec 1972;56(12):863-74. [Medline].
Van Buskirk EM, Lessell S, Friedman E. Pigmentary epitheliopathy and erythema nodosum. Arch Ophthalmol. Mar 1971;85(3):369-72. [Medline].
Fine HF, Kim E, Flynn TE, Gomes NL, Chang S. Acute posterior multifocal placoid pigment epitheliopathy following varicella vaccine. Br J Ophthalmol. Aug 26 2008;[Medline].
Hsu J, Fineman MS, Kaiser RS. Optical coherence tomography findings in acute retinal pigment epitheliitis. Am J Ophthalmol. Jan 2007;143(1):163-5. [Medline].
Matsuo T, Horikoshi T, Nagai C. Acute posterior multifocal placoid pigment epitheliopathy and scleritis in a patient with pANCA-positive systemic vasculitis. Am J Ophthalmol. Apr 2002;133(4):566-8. [Medline].
Parmeggiani F, Costagliola C, D'Angelo S, Incorvaia C, Perri P, Sebastiani A. Clear cell renal cell carcinoma associated with bilateral atypical acute posterior multifocal placoid pigment epitheliopathy. Oncology. 2004;66(6):502-9. [Medline].
Ruiz Viñals AT, Buil Calvo JA, Martínez Giralto O, Castilla Céspedes M. [Acute posterior multifocal placoid pigment epitheliopathy associated with Graves-Basedow's disease]. Arch Soc Esp Oftalmol. Jul 2002;77(7):381-4. [Medline].
Thomson SP, Roxburgh ST. Acute posterior multifocal placoid pigment epitheliopathy associated with adenovirus infection. Eye. May 2003;17(4):542-4. [Medline].
Al Kawi A, Wang DZ, Kishore K, Kattah JC. A case of ischemic cerebral infarction associated with acute posterior multifocal placoid pigment epitheliopathy, CNS vasculitis, vitamin B(12) deficiency and homocysteinemia. Cerebrovasc Dis. 2004;18(4):338-9. [Medline].
Bugnone AN, Hartker F, Shapiro M, Pineless HS, Velez G. Acute and chronic brain infarcts on MR imaging in a 20-year-old woman with acute posterior multifocal placoid pigment epitheliopathy. AJNR Am J Neuroradiol. Jan 2006;27(1):67-9. [Medline].
de Vries JJ, den Dunnen WF, Timmerman EA, Kruithof IG, De Keyser J. Acute posterior multifocal placoid pigment epitheliopathy with cerebral vasculitis: a multisystem granulomatous disease. Arch Ophthalmol. Jun 2006;124(6):910-3. [Medline].
Suzuki S, Mizota A, Adachi-Usami E. A case of hemophagocytic syndrome with retinal changes resembling acute posterior multifocal placoid pigment epitheliopathy. Retina. Apr 2002;22(2):219-22. [Medline].
Wolf MD, Alward WL, Folk JC. Long-term visual function in acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. Jun 1991;109(6):800-3. [Medline].
Saraux H, Pelosse B. Acute posterior multifocal placoid pigment epitheliopathy. A long-term follow-up. Ophthalmologica. 1987;194(4):161-3. [Medline].
Taich A, Johnson MW. A syndrome resembling acute posterior multifocal placoid pigment epitheliopathy in older adults. Retina. Feb 2009;29(2):149-56. [Medline].
Bowie EM, Sletten KR, Kayser DL, Folk JC. Acute posterior multifocal placoid pigment epitheliopathy and choroidal neovascularization. Retina. Apr-May 2005;25(3):362-4. [Medline].
Yenerel NM, Gorgun E, Dinc UA, Oncel M. Treatment of cystoid macular edema due to acute posterior multifocal placoid pigment epitheliopathy. Ocul Immunol Inflamm. Jan-Feb 2008;16(1):67-71. [Medline].
Teyssot N, Bodaghi B, Cassoux N, Fardeau C, Le Mer Y, Ullern M, et al. [Acute posterior multifocal placoid pigment epitheliopathy, serpiginous and multifocal choroiditis: etiological and therapeutic management]. J Fr Ophtalmol. May 2006;29(5):510-8. [Medline].
Krill AE, Deutman AF. Acute retinal pigment epitheliitus. Am J Ophthalmol. Aug 1972;74(2):193-205. [Medline].
Jamison RR. Acute retinal pigment epitheliitis with macular edema. Ann Ophthalmol. Mar 1979;11(3):359-61. [Medline].
Luttrull JK, Chittum ME. Acute retinal pigment epitheliitis. Am J Ophthalmol. Sep 1995;120(3):389-91. [Medline].
Luttrull JK. Acute retinal pigment epitheliitis. Am J Ophthalmol. Jan 1997;123(1):127-9. [Medline].
Bialasiewicz AA, Schonherr U. [Choriocapillaritis (so-called pigment epitheliitis) in Borrelia burgdorferi seroconversion]. Klin Monatsbl Augenheilkd. Jun 1990;196(6):481-3. [Medline].
Quillen DA, Zurlo JJ, Cunningham D, Blankenship GW. Acute retinal pigment epitheliitis and hepatitis C. Am J Ophthalmol. Jul 15 1994;118(1):120-1. [Medline].
Blanco-Rivera C, Campos-García S. [Acute retinal pigment epitheliitis: a case report]. Arch Soc Esp Oftalmol. Jul 2007;82(7):451-3. [Medline].
Piermarocchi S, Corradini R, Midena E, Segato T. Correlation between retinal pigment epitheliitis and central serous chorioretinopathy. Ann Ophthalmol. May 1983;15(5):425-8. [Medline].
Gilhotra JS, Gilhotra AK, Holdaway IM, Donaldson ML. Acute retinal pigment epitheliitis associated with intravenous bisphosphonate. Br J Ophthalmol. Jun 2006;90(6):798-9. [Medline].
Prost M. Long-term observations of patients with acute retinal pigment epitheliitis. Ophthalmologica. 1989;199(2-3):84-9. [Medline].
Chittum ME, Kalina RE. Acute retinal pigment epitheliitis. Ophthalmology. Sep 1987;94(9):1114-9. [Medline].
Lim JI, Kokame GT, Douglas JP. Multiple evanescent white dot syndrome in older patients. Am J Ophthalmol. Jun 1999;127(6):725-8. [Medline].
Jampol LM, Sieving PA, Pugh D, et al. Multiple evanescent white dot syndrome. I. Clinical findings. Arch Ophthalmol. May 1984;102(5):671-4. [Medline].
Fine HF, Spaide RF, Ryan EH Jr, Matsumoto Y, Yannuzzi LA. Acute zonal occult outer retinopathy in patients with multiple evanescent white dot syndrome. Arch Ophthalmol. Jan 2009;127(1):66-70. [Medline].
Aaberg TM, Campo RV, Joffe L. Recurrences and bilaterality in the multiple evanescent white-dot syndrome. Am J Ophthalmol. Jul 15 1985;100(1):29-37. [Medline].
Asano T, Kondo M, Kondo N, Ueno S, Terasaki H, Miyake Y. High prevalence of myopia in Japanese patients with multiple evanescent white dot syndrome. Jpn J Ophthalmol. Sep-Oct 2004;48(5):486-9. [Medline].
Barile GR, Reppucci VS, Schiff WM, Wong DT. Circumpapillary chorioretinopathy in multiple evanescent white-dot syndrome. Retina. 1997;17(1):75-7. [Medline].
Luttrull JK, Marmor MF, Nanda M. Progressive confluent circumpapillary multiple evanescent white-dot syndrome. Am J Ophthalmol. Sep 1999;128(3):378-80. [Medline].
Ray S, Loewenstein J. Atypical manifestation of multiple evanescent white dot syndrome with large peripapillary lesion. Arch Ophthalmol. Dec 2003;121(12):1794-6. [Medline].
Yenerel NM, Kucumen B, Gorgun E, Dinc UA. Atypical presentation of multiple evanescent white dot syndrome (MEWDS). Ocul Immunol Inflamm. May-Jun 2008;16(3):113-5. [Medline].
Huang J, Spaide R. Appearance of brown areas after resolution of the acute phase of multiple evanescent white dot syndrome. Retina. Oct 2004;24(5):814-6. [Medline].
Callanan D, Gass JD. Multifocal choroiditis and choroidal neovascularization associated with the multiple evanescent white dot and acute idiopathic blind spot enlargement syndrome. Ophthalmology. Nov 1992;99(11):1678-85. [Medline].
McCollum CJ, Kimble JA. Peripapillary subretinal neovascularization associated with multiple evanescent white-dot syndrome. Arch Ophthalmol. Jan 1992;110(1):13-4. [Medline].
Khurana RN, Albini T, Dea MK, Rao NA, Lim JI. Atypical presentation of multiple evanescent white dot syndrome involving granular lesions of varying size. Am J Ophthalmol. May 2005;139(5):935-7. [Medline].
Furino C, Boscia F, Cardascia N, Alessio G, Sborgia C. Fundus autofluorescence and multiple evanescent white dot syndrome. Retina. Jan 2009;29(1):60-3. [Medline].
Li D, Kishi S. Restored photoreceptor outer segment damage in multiple evanescent white dot syndrome. Ophthalmology. Apr 2009;116(4):762-70. [Medline].
Ie D, Glaser BM, Murphy RP, et al. Indocyanine green angiography in multiple evanescent white-dot syndrome. Am J Ophthalmol. Jan 15 1994;117(1):7-12. [Medline].
Desarnaulds AB, Borruat FX, Herbort CP, de Courten C. [Indocyanine green angiography in "multiple evanescent white dot syndrome" (MEWDS)]. Klin Monatsbl Augenheilkd. May 1998;212(5):318-20. [Medline].
Borruat FX, Auer C, Piguet B. Choroidopathy in multiple evanescent white dot syndrome. Arch Ophthalmol. Dec 1995;113(12):1569-71. [Medline].
Obana A, Kusumi M, Miki T. Indocyanine green angiographic aspects of multiple evanescent white dot syndrome. Retina. 1996;16(2):97-104. [Medline].
Tsukamoto E, Yamada T, Kadoi C, Hayasaka S, Nagaki Y, Hayasaka Y. Hypofluorescent spots on indocyanine green angiography at the recovery stage in multiple evanescent white dot syndrome. Ophthalmologica. 1999;213(5):336-8. [Medline].
Yen MT, Rosenfeld PJ. Persistent indocyanine green angiographic findings in multiple evanescent white dot syndrome. Ophthalmic Surg Lasers. Mar-Apr 2001;32(2):156-8. [Medline].
Stanga PE, Lim JI, Hamilton P. Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update. Ophthalmology. Jan 2003;110(1):15-21; quiz 22-3. [Medline].
Kanis MJ, van Norren D. Integrity of foveal cones in multiple evanescent white dot syndrome assessed with OCT and foveal reflection analyser. Br J Ophthalmol. Jun 2006;90(6):795-6. [Medline].
Sikorski BL, Wojtkowski M, Kaluzny JJ, Szkulmowski M, Kowalczyk A. Correlation of spectral optical coherence tomography with fluorescein and indocyanine green angiography in multiple evanescent white dot syndrome. Br J Ophthalmol. Nov 2008;92(11):1552-7. [Medline].
Spaide RF, Koizumi H, Freund KB. Photoreceptor outer segment abnormalities as a cause of blind spot enlargement in acute zonal occult outer retinopathy-complex diseases. Am J Ophthalmol. Jul 2008;146(1):111-20. [Medline].
Li D, Kishi S. Restored photoreceptor outer segment damage in multiple evanescent white dot syndrome. Ophthalmology. Apr 2009;116(4):762-70. [Medline].
Amin HI. Optical coherence tomography findings in multiple evanescent white dot syndrome. Retina. Apr 2006;26(4):483-4. [Medline].
Horiguchi M, Miyake Y, Nakamura M, Fujii Y. Focal electroretinogram and visual field defect in multiple evanescent white dot syndrome. Br J Ophthalmol. Jul 1993;77(7):452-5. [Medline].
Yamamoto S, Hayashi M, Tsuruoka M, Yamamoto T, Tsukahara I, Takeuchi S. S-cone electroretinograms in multiple evanescent white dot syndrome. Doc Ophthalmol. Mar 2003;106(2):117-20. [Medline].
Chen D, Martidis A, Baumal CR. Transient multifocal electroretinogram dysfunction in multiple evanescent white dot syndrome. Ophthalmic Surg Lasers. May-Jun 2002;33(3):246-9. [Medline].
Chen JY, Hood DC, Odel JG, Behrens MM. The effects of retinal abnormalities on the multifocal visual evoked potential. Invest Ophthalmol Vis Sci. Oct 2006;47(10):4378-85. [Medline].
Feigl B, Haas A, El-Shabrawi Y. Multifocal ERG in multiple evanescent white dot syndrome. Graefes Arch Clin Exp Ophthalmol. Aug 2002;240(8):615-21. [Medline].
Dodwell DG, Jampol LM, Rosenberg M, et al. Optic nerve involvement associated with the multiple evanescent white- dot syndrome. Ophthalmology. Jul 1990;97(7):862-8. [Medline].
Hamed LM, Glaser JS, Gass JD, Schatz NJ. Protracted enlargement of the blind spot in multiple evanescent white dot syndrome. Arch Ophthalmol. Feb 1989;107(2):194-8. [Medline].
Boscarino MA, Johnson TM. Microperimetry in multiple evanescent white dot syndrome. Can J Ophthalmol. Oct 2007;42(5):743-5. [Medline].
Huang HJ, Yamazaki H, Kawabata H, et al. Multifocal electroretinogram in multiple evanescent white dot syndrome. Doc Ophthalmol. 1996-97;92(4):301-9. [Medline].
Baglivo E, Safran AB, Borruat FX. Multiple evanescent white dot syndrome after hepatitis B vaccine. Am J Ophthalmol. Sep 1996;122(3):431-2. [Medline].
Fine L, Fine A, Cunningham ET Jr. Multiple evanescent white dot syndrome following hepatitis a vaccination. Arch Ophthalmol. Dec 2001;119(12):1856-8. [Medline].
Stangos A, Zaninetti M, Petropoulos I, Baglivo E, Pournaras C. Multiple evanescent white dot syndrome following simultaneous hepatitis-A and yellow fever vaccination. Ocul Immunol Inflamm. Oct 2006;14(5):301-4. [Medline].
Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol. Apr 2008;30(2):127-34. [Medline].
Chung YM, Yeh TS, Liu JH. Increased serum IgM and IgG in the multiple evanescent white-dot syndrome. Am J Ophthalmol. Aug 15 1987;104(2):187-8. [Medline].
Borruat FX, Herbort CP, Spertini F, Desarnaulds AB. HLA typing in patients with multiple evanescent white dot syndrome (MEWDS). Ocul Immunol Inflamm. Mar 1998;6(1):39-41. [Medline].
Bryan RG, Freund KB, Yannuzzi LA, Spaide RF, Huang SJ, Costa DL. Multiple evanescent white dot syndrome in patients with multifocal choroiditis. Retina. Jun 2002;22(3):317-22. [Medline].
Shah GK, Kleiner RC, Augsburger JJ, Gill MK, Jampol LM. Primary intraocular lymphoma seen with transient white fundus lesions simulating the multiple evanescent white dot syndrome. Arch Ophthalmol. Apr 2001;119(4):617-20. [Medline].
Landolfi M, Bhagat N, Langer P, Rescigno R, Mirani N, Gass JD, et al. Penetrating trauma associated with findings of multiple evanescent white dot syndrome in the second eye: coincidence or an atypical case of sympathetic ophthalmia?. Retina. Aug 2004;24(4):637-45. [Medline].
Fahim DK, Bucher R, Johnson MW. The elusive nature of primary intraocular lymphoma. J Neuroophthalmol. Mar 2005;25(1):33-6. [Medline].
Tsai L, Jampol LM, Pollock SC, Olk J. Chronic recurrent multiple evanescent white dot syndrome. Retina. 1994;14(2):160-3. [Medline].
Oh KT, Christmas NJ, Russell SR. Late recurrence and choroidal neovascularization in multiple evanescent white dot syndrome. Retina. 2001;21(2):182-4. [Medline].
Machida S, Fujiwara T, Murai K, Kubo M, Kurosaka D. Idiopathic choroidal neovascularization as an early manifestation of inflammatory chorioretinal diseases. Retina. May 2008;28(5):703-10. [Medline].
Figueroa MS, Ciancas E, Mompean B, Quereda C. Treatment of multiple evanescent white dot syndrome with cyclosporine. Eur J Ophthalmol. Jan-Mar 2001;11(1):86-8. [Medline].
Takahashi Y, Ataka S, Wada S, Kohno T, Nomura Y, Shiraki K. A case of multiple evanescent white dot syndrome treated by steroid pulse therapy. Osaka City Med J. Dec 2006;52(2):83-6. [Medline].
Matsumoto Y, Haen SP, Spaide RF. The white dot syndromes. Compr Ophthalmol Update. Jul-Aug 2007;8(4):179-200; discussion 203-4. [Medline].
Rouvas AA, Ladas ID, Papakostas TD, Moschos MM, Vergados I. Intravitreal ranibizumab in a patient with choroidal neovascularization secondary to multiple evanescent white dot syndrome. Eur J Ophthalmol. Nov-Dec 2007;17(6):996-9. [Medline].
FRANCESCHETTI A, BABEL J. La choriorétinite en taches de bougie, manifestation de la maladie de Besnier-Boeck. Ophthalmologica. Oct-Nov 1949;118(4-5):701-10. [Medline].
Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol. Jan 1980;89(1):31-45. [Medline].
Gasch AT, Smith JA, Whitcup SM. Birdshot retinochoroidopathy. Br J Ophthalmol. Feb 1999;83(2):241-9. [Medline].
Barondes MJ, Fastenberg DM, Schwartz PL, Rosen DA. Peripheral retinal neovascularization in birdshot retinochoroidopathy. Ann Ophthalmol. Aug 1989;21(8):306-8. [Medline].
Soubrane G, Coscas G, Binaghi M, Bernard JA. Birdshot retinochoroidopathy and subretinal new vessels. Br J Ophthalmol. Jul 1983;67(7):461-7. [Medline].
Guex-Crosier Y, Herbort CP. Prolonged retinal arterio-venous circulation time by fluorescein but not by indocyanine green angiography in birdshot chorioretinopathy. Ocul Immunol Inflamm. Sep 1997;5(3):203-6. [Medline].
Fardeau C, Herbort CP, Kullmann N, et al. Indocyanine green angiography in birdshot chorioretinopathy. Ophthalmology. Oct 1999;106(10):1928-34. [Medline].
Hirose T, Katsumi O, Pruett RC, et al. Retinal function in birdshot retinochoroidopathy. Acta Ophthalmol (Copenh). Jun 1991;69(3):327-37. [Medline].
de Courten C, Herbort CP. Potential role of computerized visual field testing for the appraisal and follow-up of birdshot chorioretinopathy. Arch Ophthalmol. Oct 1998;116(10):1389-91. [Medline].
Nussenblatt RB, Mittal KK, Ryan S, et al. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J Ophthalmol. Aug 1982;94(2):147-58. [Medline].
Priem HA, Oosterhuis JA. Birdshot chorioretinopathy: clinical characteristics and evolution. Br J Ophthalmol. Sep 1988;72(9):646-59. [Medline].
LeHoang PD, Ryan SJ. Birdshot retinochoroidopathy. In: Pepose JS, Holland GN, Wilhelmus KR, eds. Ocular Infection and Immunity. Mosby-Year Book;1995:570-78.
Rothova A, Van Schooneveld MJ. The end stage of birdshot retinochoroidopathy. Br J Ophthalmol. Nov 1995;79(11):1058-9. [Medline].
Kappel PJ, Monnet D, Yu F, Brezin AP, Levinson RD, Holland GN. Contrast sensitivity among patients with birdshot chorioretinopathy. Am J Ophthalmol. Feb 2009;147(2):351-356.e2. [Medline].
Ladas JG, Arnold AC, Holland GN. Control of visual symptoms in two men with birdshot retinochoroidopathy using low-dose oral corticosteroid therapy. Am J Ophthalmol. Jul 1999;128(1):116-8. [Medline].
Greenwood AJ, Stanford MR, Graham EM. The role of azathioprine in the management of retinal vasculitis. Eye. 1998;12 (Pt 5):783-8. [Medline].
Silverstein BE, Wong IG. Reduction of cyclosporine dosage with ketoconazole in a patient with birdshot retinochoroidopathy. Am J Ophthalmol. Jan 1998;125(1):106-8. [Medline].
Nussenblatt RB. Reduction of cyclosporine dosage with ketoconazole in a patient with birdshot retinochoroidopathy. Am J Ophthalmol. Nov 1998;126(5):742. [Medline].
LeHoang P, Cassoux N, George F, et al. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. Ocul Immunol Inflamm. Mar 2000;8(1):49-57. [Medline].
Junius P. Seltene augenspielgelbider zum klinischen phanomen der retinitis exsuditiva Coats und der retinochoroiditis "parapapillaris". Arch Augenheilk. 1932;106:475.
Schatz H, Maumenee AE, Patz A. Geographical helicoid peripapillary choroidopathy: Clinical presentation and fluorescein angiographic findings. Trans Am Acad Ophthalmol Otolaryngol. 1974;78:747-61.
Hamilton AM, Bird AC. Geographical choroidopathy. Br J Ophthalmol. Sep 1974;58(9):784-97. [Medline].
Masi RJ, O''Connor GR, Kimura SJ. Anterior uveitis in geographic or serpiginous choroiditis. Am J Ophthalmol. Aug 1978;86(2):228-32. [Medline].
Abu el-Asrar AM. Serpiginous (geographical) choroiditis. Int Ophthalmol Clin. Spring 1995;35(2):87-91. [Medline].
Ciulla TA, Gragoudas ES. Serpiginous choroiditis. Int Ophthalmol Clin. Winter 1996;36(1):135-43. [Medline].
Chisholm IH, Gass JD, Hutton WL. The late stage of serpiginous (geographic) choroiditis. Am J Ophthalmol. Sep 1976;82(3):343-51. [Medline].
Jampol LM, Orth D, Daily MJ, Rabb MF. Subretinal neovascularization with geographic (serpiginous) choroiditis. Am J Ophthalmol. Oct 1979;88(4):683-9. [Medline].
Blumenkranz MS, Gass JD, Clarkson JG. Atypical serpiginous choroiditis. Arch Ophthalmol. Nov 1982;100(11):1773-5. [Medline].
Laatikainen L, Erkkila H. Subretinal and disc neovascularisation in serpiginous choroiditis. Br J Ophthalmol. May 1982;66(5):326-31. [Medline].
Friberg TR. Serpiginous choroiditis with branch vein occlusion and bilateral periphlebitis. Case report. Arch Ophthalmol. May 1988;106(5):585-6. [Medline].
Wu JS, Lewis H, Fine SL, et al. Clinicopathologic findings in a patient with serpiginous choroiditis and treated choroidal neovascularization. Retina. 1989;9(4):292-301. [Medline].
Edelsten C, Stanford MR, Graham EM. Serpiginous choroiditis: an unusual presentation of ocular sarcoidosis. Br J Ophthalmol. Jan 1994;78(1):70-1. [Medline].
Richardson RR, Cooper IS, Smith JL. Serpiginous choroiditis and unilateral extrapyramidal dystonia. Ann Ophthalmol. Jan 1981;13(1):15-9. [Medline].
King DG, Grizzard WS, Sever RJ, Espinoza L. Serpiginous choroidopathy associated with elevated factor VIII-von Willebrand factor antigen. Retina. 1990;10(2):97-101. [Medline].
Secchi AG, Tognon MS, Maselli C. Cyclosporine-A in the treatment of serpiginous choroiditis. Int Ophthalmol. Oct 1990;14(5-6):395-9. [Medline].
Hoyng C, Tilanus M, Deutman A. Atypical central lesions in serpiginous choroiditis treated with oral prednisone. Graefes Arch Clin Exp Ophthalmol. Feb 1998;236(2):154-6. [Medline].
Hooper PL, Kaplan HJ. Triple agent immunosuppression in serpiginous choroiditis. Ophthalmology. Jun 1991;98(6):944-51; discussion 951-2. [Medline].
Goldberg MA, Kazacos KR, Boyce WM, et al. Diffuse unilateral subacute neuroretinitis. Morphometric, serologic, and epidemiologic support for Baylisascaris as a causative agent. Ophthalmology. Nov 1993;100(11):1695-701. [Medline].
de Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology. Aug 1995;102(8):1183-6. [Medline].
Abu El-Asrar AM, Aljazairy AH. Acute posterior multifocal placoid pigment epitheliopathy with retinal vasculitis and papillitis. Eye. Sep 2002;16(5):642-4. [Medline].
Amin HI. Optical coherence tomography findings in multiple evanescent white dot syndrome. Retina. Apr 2006;26(4):483-4. [Medline].
Arevalo JF, Shields CL, Shields JA. Giant nodular posterior scleritis simulating choroidal melanoma and birdshot retinochoroidopathy. Ophthalmic Surg Lasers Imaging. Sep-Oct 2003;34(5):403-5. [Medline].
Bodaghi B, Rozenberg F, Cassoux N, Fardeau C, LeHoang P. Nonnecrotizing herpetic retinopathies masquerading as severe posterior uveitis. Ophthalmology. Sep 2003;110(9):1737-43. [Medline].
Bouchenaki N, Cimino L, Auer C, Tao Tran V, Herbort CP. Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography. Klin Monatsbl Augenheilkd. Apr 2002;219(4):243-9. [Medline].
Burés-Jelstrup A, Adán A, Casaroli-Marano R. [Acute posterior multifocal placoid pigment epitheliopathy. Study of 16 cases]. Arch Soc Esp Oftalmol. May 2007;82(5):291-7. [Medline].
Cunningham ET Jr, Sabrosa NA, Pavesio CE. Posterior scleritis mimicking birdshot retinochoroidopathy. Eye. Apr 2001;15:231-3. [Medline].
Daniele S, Daniele C, Ferri C. Association of peripapillary scars with lesions characteristic of multiple evanescent white-dot syndrome. Ophthalmologica. 1995;209(4):217-9. [Medline].
Desarnaulds AB, Borruat FX, Herbort CP, Spertini F. [Multiple evanescent white dot syndrome: a genetic predisposition?]. Klin Monatsbl Augenheilkd. May 1996;208(5):301-2. [Medline].
Dolan FM, Gavin M, Parks S, Keating D. Recovery of visual function in a patient with birdshot chorioretinitis. Br J Ophthalmol. May 2003;87(5):657-8. [Medline].
Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. Aug 1968;80(2):177-85. [Medline].
Gass JD. Acute zonal occult outer retinopathy: Donders Lecture: The Netherlands Ophthalmological Society, Maastricht, Holland, June 19, 1992. 1993. Retina. Dec 2003;23(6 Suppl):79-97. [Medline].
Gass JD. Overlap among acute idiopathic blind spot enlargement syndrome and other conditions. Arch Ophthalmol. Nov 2001;119(11):1729-31. [Medline].
Gross NE, Yannuzzi LA, Freund KB, Spaide RF, Amato GP, Sigal R. Multiple evanescent white dot syndrome. Arch Ophthalmol. Apr 2006;124(4):493-500. [Medline].
Gross NE, Yannuzzi LA, Freund KB, Spaide RF, Amato GP, Sigal R. Multiple evanescent white dot syndrome. Arch Ophthalmol. Apr 2006;124(4):493-500. [Medline].
Howe LJ, Woon H, Graham EM, et al. Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study. Ophthalmology. May 1995;102(5):790-8. [Medline].
Hsu CT, Harlan JB, Goldberg MF, Dunn JP. Acute posterior multifocal placoid pigment epitheliopathy associated with a systemic necrotizing vasculitis. Retina. Feb 2003;23(1):64-8. [Medline].
Ikeda N, Ikeda T, Nagata M, Tano R, Mimura O. Location of lesions in multiple evanescent white dot syndrome and the cause of the hypofluorescent spots observed by indocyanine green angiography. Graefes Arch Clin Exp Ophthalmol. Mar 2001;239(3):242-7. [Medline].
Kanis MJ, van Norren D. Integrity of foveal cones in multiple evanescent white dot syndrome assessed with OCT and foveal reflection analyser. Br J Ophthalmol. Jun 2006;90(6):795-6. [Medline].
Kiss S, Anzaar F, Stephen Foster C. Birdshot retinochoroidopathy. Int Ophthalmol Clin. Spring 2006;46(2):39-55. [Medline].
Laghmari M, Boutimzine N, Karim A, Alami Moudni M, Benchrif MZ, Essakalli HN, et al. [Posterior scleritis simulating acute posterior multifocal placoid pigment epitheliopathy]. J Fr Ophtalmol. Feb 2004;27(2):174-8. [Medline].
Levinson RD, Brezin A, Rothova A, Accorinti M, Holland GN. Research criteria for the diagnosis of birdshot chorioretinopathy: results of an international consensus conference. Am J Ophthalmol. Jan 2006;141(1):185-7. [Medline].
Lim L, Harper A, Guymer R. Choroidal lesions preceding symptom onset in birdshot chorioretinopathy. Arch Ophthalmol. Jul 2006;124(7):1057-8. [Medline].
Mathura JR Jr, Jampol LM, Daily MJ. Multifocal choroiditis and acute posterior multifocal placoid pigment epitheliopathy occurring in the same patient. Arch Ophthalmol. Dec 2004;122(12):1881-2. [Medline].
Mensah E, Vafidis GC. Acute posterior multifocal placoid pigment epitheliopathy in a 7-year-old girl. J Pediatr Ophthalmol Strabismus. Jul-Aug 2002;39(4):239-41. [Medline].
Monnet D, Brézin AP. Birdshot chorioretinopathy. Curr Opin Ophthalmol. Dec 2006;17(6):545-50. [Medline].
Monnet D, Brézin AP, Holland GN, Yu F, Mahr A, Gordon LK, et al. Longitudinal cohort study of patients with birdshot chorioretinopathy. I. Baseline clinical characteristics. Am J Ophthalmol. Jan 2006;141(1):135-42. [Medline].
Nguyen MH, Witkin AJ, Reichel E, Ko TH, Fujimoto JG, Schuman JS, et al. Microstructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical coherence tomography. Retina. Apr-May 2007;27(4):414-8. [Medline].
Oh KT, Folk JC, Maturi RK, Moore P, Kardon RH. Multifocal electroretinography in multifocal choroiditis and the multiple evanescent white dot syndrome. Retina. 2001;21(6):581-9. [Medline].
Postelmans L, Pasteels B, Coquelet P, et al. Photodynamic therapy for subfoveal classic choroidal neovascularization related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Ocul Immunol Inflamm. Sep-Oct 2005;13(5):361-6. [Medline].
Quillen DA, Davis JB, Gottlieb JL, Blodi BA, Callanan DG, Chang TS, et al. The white dot syndromes. Am J Ophthalmol. Mar 2004;137(3):538-50. [Medline].
Quillen DA, Davis JB, Gottlieb JL, Blodi BA, Callanan DG, Chang TS, et al. The white dot syndromes. Am J Ophthalmol. Mar 2004;137(3):538-50. [Medline].
Read RW, Rao NA, Sharma OP. Sarcoid choroiditis initially diagnosed as birdshot choroidopathy. Sarcoidosis Vasc Diffuse Lung Dis. Mar 2000;17(1):85-6. [Medline].
Saito W, Yamamoto S, Mitamura Y, Takeuchi S. [Birdshot chorioretinopathy--a case report and a case study in Japanese patients]. Nippon Ganka Gakkai Zasshi. Apr 2002;106(4):229-35. [Medline].
Scheufele T. 2005.
Schneider U, Inhoffen W, Gelisken F. Indocyanine green angiography in a case of unilateral recurrent posterior acute multifocal placoid pigment epitheliopathy. Acta Ophthalmol Scand. Feb 2003;81(1):72-5. [Medline].
Shah KH, Levinson RD, Yu F, Goldhardt R, Gordon LK, Gonzales CR, et al. Birdshot chorioretinopathy. Surv Ophthalmol. Nov-Dec 2005;50(6):519-41. [Medline].
Sikorski BL, Wojtkowski M, Kaluzny JJ, Szkulmowski M, Kowalczyk A. Correlation of spectral optical coherence tomography with fluorescein and indocyanine green angiography in multiple evanescent white dot syndrome. Br J Ophthalmol. Nov 2008;92(11):1552-7. [Medline].
Sommer S, Badet JC, Zaoui M, Naoun-Hubert I, Rozot P. [Birdshot chorioretinopathy associated with tamoxifen retinal toxicity]. J Fr Ophtalmol. May 2000;23(5):494-7. [Medline].
Tellier Z. Human immunoglobulins in intraocular inflammation. Ann N Y Acad Sci. Sep 2007;1110:337-47. [Medline].
Uthman I, Najjar DM, Kanj SS, Bashshur Z. Anticardiolipin antibodies in acute multifocal posterior placoid pigment epitheliopathy. Ann Rheum Dis. Jul 2003;62(7):687-8. [Medline].
Volpe NJ, Rizzo JF 3rd, Lessell S. Acute idiopathic blind spot enlargement syndrome: a review of 27 new cases. Arch Ophthalmol. Jan 2001;119(1):59-63. [Medline].
Willermain F, Greiner K, Forrester JV. Atypical end-stage birdshot retinochoroidopathy. Ocul Immunol Inflamm. Dec 2003;11(4):305-7. [Medline].
Yang DS, Hilford DJ, Conrad D. Acute posterior multifocal placoid pigment epitheliopathy after meningococcal C conjugate vaccine. Clin Experiment Ophthalmol. Apr 2005;33(2):219-21. [Medline].
Further Reading
Clinical trials:
Evaluation of Birdshot Retine Choroidopathy Treatment by Either Steroid or Interferon alpha2a (BIRDFERON)
Tracking Optical Coherence Tomography
Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of Age-Related Macular Degeneration (AMD) and Other Related Maculopathy (FVF4140S)
Keywords
multifocal choroidopathy syndromes, choroid, choroidal, choroiditis, panuveitis, choroidal neovascularization, retinal pigment epithelium, multifocal choroiditis, acute posterior multifocal placoid pigment epitheliopathy, acute retinal pigment epithelitis, Krill disease, multiple evanescent white dot syndrome, birdshot retinochoroidopathy, serpiginous choroiditis, diffuse unilateral subacute neuroretinitis
