The White Dot Syndromes

Yoko Matsumoto, MD, PHD; Sebastian P. Haen, MD; Richard F. Spaide, MD

Disclosures

Compr Ophthalmol Update. 2007;8(4):179-200. 

In This Article

Birdshot Chorioretinopathy

Birdshot chorioretinopathy, which was first reported by Ryan and Maumenee in 1980 using the term birdshot retinochoroidopathy, shows an average age of onset of 50 years.[71] In retrospect, a number of patients in this series probably had conditions other than actual birdshot chorioretinopathy. A slight gender preference to women has been reported in some,[5,64,65] but not all, studies.[66,67,68,69] Approximately 95% of patients with birdshot chorioretinopathy are HLAA[29] seropositive,[70] with birdshot chorioretinopathy having one of the highest associations with an HLA haplotype of any known disease. The incidence in people of Northern European descent is slightly higher than in other populations.[71]

Birdshot chorioretinopathy is a rare intraocular inflammatory disorder representing about 1% to 2% of cases referred to specialized uveitis clinics.[72] The etiology of birdshot chorioretinopathy remains unknown. The strong association with HLAA29[66,68,73,74] implies a potential for a genetic predisposition to react to an environmental or infectious stimulus in a phenotypically stereotypic way. No systemic disease has been formally associated with birdshot chorioretinopathy, although fundus lesions caused by sarcoidosis can closely mimic those seen in birdshot chorioretinopathy to the point where patients have been diagnosed with birdshot chorioretinopathy for years prior to being diagnosed with sarcoidosis.[75,76] Since being associated with HLA-A29, which is also found in diseases of the rheumatoid spectrum, a high incidence of vascular diseases was reported in patients with birdshot chorioretinopathy.[71,77,78]

The most common symptoms are blurred vision, floaters, nyctalopia, photopsias, and decreased color vision. Some patients can be asymptomatic at the time of diagnosis, and some of them show symptoms before signs of the disease appear.[71] The diagnostic criteria are (1) minimal, if any anterior segment inflammation; (2) vitritis; (3) leakage from retinal vessels at the posterior pole that can be associated with secondary CME; (4) optic disk edema; (5) cream-colored spots of depigmentation at the posterior pole; and (6) painless eye.[64,79]

Patients with birdshot chorioretinopathy present with bilateral, multiple cream or yellowish-white lesions varying in size from onefourth to 1 disk diameter (Figure 4). The spots tend to be oval, with the longer diameter radiating from the optic nerve to the periphery. There are two different types of lesions seen in birdshot chorioretinopathy. The acute lesions are yellowish-white opacifications of the inner choroid that may also involve the RPE. These resolve and leave a depigmented region of similar size through which the underlying larger choroidal vessels are seen.

The acute lesions are responsive to aggressive treatment, while the depigmented resolved lesions are not. There is usually a concurrent vitritis. The anterior segment may be quiet. There may be various amounts of papillitis, the amount of which correlates to the amount of vitritis present. Patients with longstanding vitritis also have concurrent retinal vasculitis, both of which may be contributory to the CME commonly seen in these patients. Additional sequelae include epiretinal membranes, recurrent vitreous hemorrhage, retinal neovascularization, optic atrophy, arteriolar narrowing, and subretinal neovascular membranes occurring both in the juxtapapillary and macular regions.[71]

HLA-A29 testing has a sensitivity of 96% and a specificity of 93%,[77] making it very useful in making the diagnosis of birdshot chorioretinopathy. HLA-A29 has been calculated to confer a relative risk of 224 for birdshot chorioretinopathy.[77] Additional tests for sarcoidosis are useful in ruling out this condition, which not only can mimic birdshot chorioretinopathy, but also often requires systemic treatment because of involvement of other systems. The EOG shows abnormalities with reduced rod and cone amplitudes. Visual evoked choroidal potentials may have abnormal amplitude and increased latency. Visual field testing can confirm overall depression of retinal function and scotoma.

Fluorescein angiography shows inconsistent findings, depending on the age of the lesion and the phase of the angiogram. Early lesions appear as hypofluorescent lesions early in the fluorescein angiographic sequence and may only have subtle findings in the late phases of the fluorescein angiogram (Figure 4). Older lesions are depigmented, which would imply that there should be a transmission defect because of the lack of blocking by the pigment within the RPE. However, older birdshot chorioretinopathy lesions are not hyperfluorescent; although there is a potential for a transmission defect due to loss of pigment, there is concurrent loss of the choriocapillaris. Thus, there is in fact a window, but there is no light behind the window (Figure 5). Indocyanine green angiography shows hypofluorescent lesions for related reasons: There is infiltration in acute lesions and loss of choriocapillaris in older lesions (Figure 5). Additional angiographic findings are related to sequelae that may occur in birdshot chorioretinopathy. Active vascular leakage along the large retinal vessels, small vessel leakage, CME, and secondary CNV can be detected. Retinal vascular narrowing occurs parallel with advancing retinal destruction.

The treatment for birdshot chorioretinopathy is not defined with certainty, but is evolving over time. In the past, it was not uncommon to avoid any treatment until complications occurred that caused loss of vision. Aggressive treatment of many white dot syndromes appears to reduce the long-term damage these diseases cause. Early aggressive treatment of birdshot chorioretinopathy can cause regression of the lesions. [Brue C, Fisher Y, Spaide RF: Bilateral choroidal neovascularization in birdshot chorioretinopathy treated with intravitreal triamcinolone and bevacizumab. Submitted to Retina, in press] These considerations lead to the treatment by some authorities at much earlier stages of disease.

At present, the lack of randomized trial results for systemic treatment creates a situation where personal opinion and experience guide treatment, often in very divergent ways. Some authors believe that systemic treatment should be initiated when the visual acuity in both eyes decreases below 20/40, which, most commonly, is due to CME. However, by the time bilateral CME and vision worse than 20/40 occur, there is already widespread damage in the fundus. Aggressive immunosuppressive therapy probably can prevent, or at least slow, the progressive damage caused by this disease.[80] Some authors have advocated laser photocoagulation for secondary CNV. More modern therapy employs the combined use of anti-inflammatory agents, systemic immunosuppressant agents, and anti-VEGF agents together.[61,62] This treatment approach avoids iatrogenic destruction of the perifoveal macula and helps to suppress formation of CNV from neighboring sites. Alternate choices include PDT, but we have seen patients with inflammatory diseases develop widespread collateral damage with PDT alone.

Patients without severe complications can have systemic immunosuppressive agents instituted along with low-dose corticosteroids. If there is a more acute problem, the same approach is taken, except that the corticosteroid dose is increased. It is not uncommon to administer local corticosteroids to help reduce the need for as high a dose of systemic corticosteroids. Cyclosporine,[69,81,82] azathioprine, methotrexate, and mycophenolate mofetil have been reported to be beneficial.[83] These drugs can control vitreous and prevent recurrent inflammation; they can even improve or stabilize the visual acuity.[72] Mycophenolate has a favorable efficacy versus side-effect profile, but it is expensive.[83,84,85]

Anti-TNF-α (tumor necrosis factor) therapy is a provocative possibility in helping to manage patients with uveitis that is difficult to control. The effect of anti-TNF- α therapy in chronic inflammatory eye diseases, including Behcet disease, sarcoidosis, and birdshot chorioretinopathy disease, which is uncontrolled with steroids and other immunosuppressive drugs, is reported.[86,87] The number of reported cases, however, is limited, and the controlled, randomized trials are needed to determine the effect and the usage.

With no treatment, the outcome is eventually poor in patients with birdshot chorioretinopathy. Although patients may retain enough central acuity to perform activities of daily living, there is a cumulative reduction in quality of life correlated to decreased visual field, color vision, and visual acuity. Because of the widespread destruction, patients with very advanced birdshot chorioretinopathy are difficult to rehabilitate with low-vision aides. Instituting aggressive therapy early in the disease is mandatory, as late initiation of treatment might be ineffective.

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