The causes of uveitis vary widely depending upon geographic, cultural, environmental and socioeconomic factors, and upon the regional prevalence of causative agents within the environment.¹ In many parts of the world, parasitic infections of the eye are a major cause of blindness. Diffuse unilateral subacute neuroretinitis (DUSN) is an ocular parasitic infection that usually results in severe visual loss.²

Diffuse unilateral subacute neuroretinitis has been associated clinically with two different-sized, and as of yet unidentified, nematodes, both of which appear to be capable of infiltrating the subretinal space.^3-6 The term DUSN was first used by J. Donald M. Gass, MD, in 1978. Prior to that, the condition was referred to as "unilateral wipe-out syndrome."⁷ DUSN occurs in healthy patients, mainly in children and young adults, and the clinical course is characterized by periods of activity and remission. The intraocular inflammation tends to be unilateral and diffuse, and to be characterized in its early stages by vision loss, vitritis, papillitis and clusters of multiple evanescent, gray-white outer retinal lesions. In the later stages, optic atrophy, retinal artery narrowing, diffuse pigment epithelial alterations and an abnormal electroretinogram can be seen.⁸

 

Although DUSN initially was described in the southeastern and midwestern United States and the Caribbean islands, it since has been reported in other parts of North America, in South America and in northwestern Europe.^8,9 In fact, in Brazil and other parts of South America, DUSN increasingly is considered an important cause of posterior uveitis in children and young healthy adults.^10,11

Figure 1. Color photograph of the right posterior pole of a patient with diffuse unilateral subacute neuroretinitis during the late stage showing progressive optic atrophy, narrowing of the retinal arteries and marked focal as well as diffuse degenerative changes in the pigment epithelium and retina. The patient had severe and permanent loss of vision. The intraocular worm is located approximately one disc diameter inferotemporal to the disc, and is shown at higher magnification in the insert. (All images courtesy Carlos Alexandre de Amorim Garcia, MD, PhD.)

Parasites of different sizes and several species of nematodes have been reported as the etiologic agent of DUSN (See Figure 1), including smaller nematodes such as Toxocara canis, Ancylostoma caninum, Strongyloides stercoralis, Ascaris lumbricoides, the smaller nematodes, and Baylisascaris procyonis, the larger one. However, most reports suggesting a causative organism have not provided conclusive evidence of a specific nematode.¹² In the southeastern United States, the Caribbean islands and South America, those nematodes that have been isolated have varied in length from approximately 400 to 700 µm. In the north midwestern United States, in contrast, the isolated nematodes have measured approximately 1,500 to 2,000 µm in length.^4,13 

Nevertheless, Arnaldo P. Cialdini, MD, and associates reported the first South American case of DUSN caused by a larger nematode.¹⁰ In earlier reports, serologic testing was negative in most patients with viable intraretinal nematodes, which led Dr. Gass and Robert Braunstein, MD, to suggest that Toxocara was not the causative nematode in most patients with DUSN,³ but rather that it was the dog hookworm Ancylostoma caninum, which is less than 1,000 µm in length. Kevin Kazacos, DVM, PhD, and colleagues, in contrast, suggested that the larger nematodes isolated from patients in the north midwestern United States was the raccoon ascarid, Baylisascaris procyonis.¹⁴

 

Because none of the nematodes described from patients with DUSN has ever been recovered intact, identification has been based upon a combination of careful measurement of the parasite, serologic testing and epidemiological studies, all of which have had their limitations.⁴ Such uncertainties have allowed some to suggest, based on morphology alone, that tropical varieties of T. canis and A. caninum may account for some cases of DUSN in Brazil and South America (Eduardo Cunha de Souza and associates, personal communication).

 

Recognition of DUSN early in the course of disease is extremely important, since removal or destruction of the worm may prevent further vision loss. Unfortunately, however, most patients seek treatment only after extensive damage has already been done, during late stages of the disease.

Because serologic testing has been variable, the diagnosis depends upon identification of characteristic clinical findings in conjunction with an intraocular worm.¹⁵ Clinical characteristics are manifested in early and late stages. DUSN most frequently is seen in healthy children or young adults with no significant past ocular history. The onset is frequently insidious. Some patients in the early stages of the disease complain of unilateral paracentral or central scotoma, ocular discomfort or transient obscuration of vision.^5,7 The syndrome is characterized mainly by unilateral vitreous inflammation, optic disc swelling, and the presence of gray-white lesions in the deep retina.^7,11 Early signs of DUSN often are mistaken for multifocal choroiditis, acute posterior multifocal placoid pigment epitheliopathy, multiple evanescent white dot syndrome, or nonspecific optic neuritis and papillitis (See Figure 2).

Figure 2. Color photograph of the left posterior pole of a patient with DUSN during the early stages of infection showing mild to moderate vitritis, mild optic disc edema and multiple crops of evanescent, gray-white lesions at the level of the outer retina. These lesions are typically clustered in only one segment of the fundus. The worm is often seen as motile, white, glistening, gently tapered at both ends, and varying in length from 400 to 2,000μm (arrow).

Late features of the disease include narrowing of the retinal vessels, optic nerve atrophy, and the development of focal or diffuse atrophic changes in the retinal pigment epithelium (See Figure 1).¹⁶ Although most patients with DUSN do not develop the disease in the fellow eye, bilateral DUSN has been described by Dr. de Souza and associates from Brazil.⁶

 

Systemic evaluation, serologic testing, stool examinations and peripheral blood smears are of little value in making the diagnosis of DUSN. When a worm is identified within the eye of an otherwise healthy person, unless a peripheral eosinophilia is present, no further evaluation seems warranted to make the diagnosis.¹²

Most patients with DUSN have an abnormal electroretinogram, even if tested early in the course of the disease. Electroretinogram is rarely extinguished completely, however, which can help differentiate DUSN from the tapetoretinal degenerations.^11,17 In one patient, multifocal electroretinography performed before laser treatment to destroy the worm showed decreased foveal response density, and increased parafoveal and perifoveal waveform amplitudes. Two months after laser photocoagulation of the nematode, multifocal electroretinography showed full recovery of normal findings, and visual acuity remained 20/20.¹⁸ Recently, it has been noticed that Goldmann perimetry may be useful to evaluate remaining visual field before and after treatment of the disease (Eduardo Cunha de Souza, personal communication, 2001).

In the early stages of disease, fluorescein angiography can show hypofluorescence of the focal gray-white lesions of active retinitis followed by late staining. Leakage of dye is also typically seen from the capillaries on the optic disc. Occasionally, there is evidence of prominent perivenous leakage of dye (See Figure 3).

Figure 3. Serial fluorescein angiogram performed on a patient with early stage DUSN showing areas of both vascular and retinochoroidal leakage and staining.

In more advanced stages of the disease, angiography shows greater evidence of loss of pigment from the RPE, manifested angiographically as an irregular increase in the background choroidal fluorescence.¹² Indocyanine green angiography (ICG-A) suggests that the choroid is also involved in early-stage DUSN. Choroidal infiltration, which prevents normal choroidal ICG impregnation, most probably is the physiopathogenic explanation for the hypofluorescent dark spots seen in affected eyes. The dark spots present in the initial ICG-A phase seem to either disappear or persist in the late phase of the examination. Hypofluorescent dots persisting in the late phase are interpreted as full-thickness lesions allowing no ICG diffusion; dots becoming isofluorescent in the late phase are interpreted as partial-thickness lesions progressively surrounded by ICG fluorescence.¹⁹

Early signs of DUSN often are mistaken for those of sarcoidosis and other entities that cause focal chorioretinitis including toxoplasmosis and histoplasmosis, multifocal choroiditis, serpiginous choroiditis, acute posterior multifocal placoid pigment epitheliopathy, multiple evanescent white dot syndrome, nonspecific optic neuritis and papillitis. The late stage of DUSN is often mistaken for post-traumatic chorioretinopathy, occlusive vascular disease, sarcoidosis or toxic retinopathy.^12,16

Treatment is limited in patients with DUSN. At present, treatment of a visible worm with photocoagulation seems to offer the best chance for halting worm motility and resolution of the active gray-white lesions without causing significant intraocular inflammation or toxic damage to the eye. Some improvement in vision and visual field may occur after laser treatment of the worm.²⁰ In some patients with the worm very close to the center of the fovea in which heavy photocoagulation may damage the remaining central vision, it may be possible to use very light applications of the laser to chase the worm into the mid-periphery, where it may be destroyed with less retinal damage.¹⁶

Chemotherapy with anthelmintic drugs, such as thiabendazole, may be the only treatment available when a worm cannot be visualized, but success is often difficult to document. Dr. de Souza and colleagues described 12 patients whose VA, visual field and intraocular inflammatory signs improved following treatment exclusively with high-dose oral albendazole (400 mg/d) for 30 days.²¹ Treatment with corticosteroids has shown transient suppression of the inflammation without altering the final outcome of the disease.¹⁶

Pars plana vitrectomy is not the standard of treatment for DUSN whenever laser is possible. At times, however, vitrectomy may be favorably compared to photocoagulation.¹⁶

In summary, DUSN is a potentially blinding form of uveitis caused by ocular nematode infestation. The diagnosis should be suspected in children and young adults with unilateral uveitis associated with multifocal choroiditis, disproportionate vision loss given the clinical findings, and little or transient response to corticosteroids. Definitive treatment involves destruction or removal of the nematode.