Journal of Pediatric Ophthalmology and Strabismus

Review Article 

Diffuse Unilateral Subacute Neuroretinitis

J. Fernando Arevalo, MD, FACS; Fernando A. Arevalo, BS; Reinaldo A. Garcia, MD; Carlos Alexandre de Amorim Garcia Filho, MD; Carlos Alexandre de Amorim Garcia, MD, PhD

Abstract

Diffuse unilateral subacute neuroretinitis (DUSN) is a usually unilateral inflammatory disease characterized by an insidious, usually severe loss of peripheral and central vision. Clinical characteristics are manifested in early and late stages. Parasites of different sizes and several species of nematodes have been reported as the etiology of DUSN without conclusive evidence about the specific agent. Because serologic testing has been variable, the definitive diagnosis is made when the clinical characteristics of DUSN are found in conjunction with an intraocular worm. Laser photocoagulation, pars plana vitrectomy, thiabendazole, and albendazole have been used to treat DUSN with variable success. [J Pediatr Ophthalmol Strabismus 2013;50(4):204–212.]

From the Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland (JFA); the Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia (JFA); the Clínica Oftalmológica Centro Caracas, Caracas, Venezuela (FAA); the Clínica Oftalmológica El Viñedo, Valencia, Venezuela (RAG); and the Department of Ophthalmology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil (CAAGF, CAAG).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: J. Fernando Arevalo, MD, FACS, Vitreoretinal Division, The King Khaled Eye Specialist Hospital, Al-Oruba St., P.O. Box 7191, Riyadh 11462, Kingdom of Saudi Arabia. E-mail: arevalojf@jhmi.edu

Received: May 14, 2012
Accepted: October 15, 2012
Posted Online: December 18, 2012

Abstract

Diffuse unilateral subacute neuroretinitis (DUSN) is a usually unilateral inflammatory disease characterized by an insidious, usually severe loss of peripheral and central vision. Clinical characteristics are manifested in early and late stages. Parasites of different sizes and several species of nematodes have been reported as the etiology of DUSN without conclusive evidence about the specific agent. Because serologic testing has been variable, the definitive diagnosis is made when the clinical characteristics of DUSN are found in conjunction with an intraocular worm. Laser photocoagulation, pars plana vitrectomy, thiabendazole, and albendazole have been used to treat DUSN with variable success. [J Pediatr Ophthalmol Strabismus 2013;50(4):204–212.]

From the Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland (JFA); the Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia (JFA); the Clínica Oftalmológica Centro Caracas, Caracas, Venezuela (FAA); the Clínica Oftalmológica El Viñedo, Valencia, Venezuela (RAG); and the Department of Ophthalmology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil (CAAGF, CAAG).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: J. Fernando Arevalo, MD, FACS, Vitreoretinal Division, The King Khaled Eye Specialist Hospital, Al-Oruba St., P.O. Box 7191, Riyadh 11462, Kingdom of Saudi Arabia. E-mail: arevalojf@jhmi.edu

Received: May 14, 2012
Accepted: October 15, 2012
Posted Online: December 18, 2012

Introduction

This entity was described by Gass in 1977, 1 who called it a “unilateral wipe-out syndrome.” The term diffuse unilateral subacute neuroretinitis (DUSN) was first used by Gass and Scelfo in 1978. 2 They described 29 patients with consistent features that included insidious, usually severe loss of peripheral and central vision with associated findings of vitreous inflammation, diffuse and focal epithelial derangement with relative sparing of the macula, narrowing of the retinal vessels, optic atrophy, increased retinal circulation time, and subnormal electroretinographic findings ( Figure 1 ). However, the cause of the inflammation in DUSN was still unknown.

(A–B) Patients during early stages of diffuse unilateral subacute neuroretinitis usually present mild to moderate vitritis, mild optic disc edema, and recurrent crops of evanescent, multi-focal, gray-white lesions at the level of the outer retina (arrows). These lesions are typically clustered in only one segment of the fundus. The intraocular worm is seen as a motile, white, often glistening nematode that is gently tapered at both ends and varies in length from 400 to 2,000 μm (insert in B).

Figure 1. (A–B) Patients during early stages of diffuse unilateral subacute neuroretinitis usually present mild to moderate vitritis, mild optic disc edema, and recurrent crops of evanescent, multi-focal, gray-white lesions at the level of the outer retina (arrows). These lesions are typically clustered in only one segment of the fundus. The intraocular worm is seen as a motile, white, often glistening nematode that is gently tapered at both ends and varies in length from 400 to 2,000 μm (insert in B).

In May 1978, Gass et al. reiterated his definition because the progressive unilateral visual loss was believed to be secondary to inflammation of the retina, retinal vessels, retinal pigment epithelium (RPE), and optic nerve head. 3 In 1983, Gass and Braunstein observed a nematode in two patients with DUSN. 4 On further searching of the literature, Gass was able to identify previously reported cases of similar nematodes that produced the same clinical picture appearing as early as 1952. 5 Hence a syndrome of initially unknown cause that was classified only by clinical description was later found to be related to a nematode in the subretinal space. 6 Although evidence suggests that most patients with DUSN will not develop it in the fellow eye, bilateral cases have been reported; therefore, a more appropriate term for this ocular condition might be “diffuse subacute neuroretinitis.” 7

De Amorim Garcia Filho et al. described the clinical features and management in the largest series of patients with DUSN to date. 8 It was a retrospective study performed at the Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil, between 2003 and 2008 to describe the determinant clinical signs to DUSN and the main features related to identification of the live worm. A total of 121 patients were included. Most patients were younger than 20 years (69.42%). Visual acuity was 20/400 or worse in 86 patients (71.7%). Nine patients (7.43%) presented in the early stage and 112 patients (92.57%) presented in the late stage. Subretinal tracks (91.7%), focal alterations of the RPE (89.3%), small white spots (80.2%), and optic nerve atrophy (76.9%) were the most frequent clinical features. The subretinal worm was identified in 48 patients (39.66%), and laser treatment to destroy it was performed in all cases. The most common location of the nematode was the posterior pole (21 patients). It was observed that the younger the age, the higher the indices of larvae identification ( P = .022). Multifocal yellow-white lesions and vitritis were correlated with identification of the worm ( P = .001). Mean logarithm of the minimum angle of resolution visual acuity was 1.466 (20/600) and 1.281 (20/400) before and after laser treatment, respectively ( P < .005). The authors concluded that identification of clinical signs and diagnosis of DUSN in its early stage, followed by prompt location and destruction of the worm by photocoagulation, may improve the vision of affected patients. 8

The objective of this review is to describe the posterior pole manifestations of DUSN and its etiology, mode of transmission, diagnosis and pathogenesis, ancillary tests, differential diagnosis, and management.

Etiologic Agent

Parasites of different sizes and several species of nematodes have been reported as the etiologic agent of DUSN, including Toxocara canis, Baylisascaris procyonis , and Ancylostoma caninum , and most of these reports do not present conclusive evidence about the specific agent. In the southeastern United States, the Caribbean islands, and South America, the nematode varies in length from approximately 400 to 700 μm. In the other endemic area, the north midwestern United States, it measures approximately 1,500 to 2,000 μm in length. 9 However, Moraes et al. reported the first South American case of DUSN caused by the larger nematode. 10 In earlier reports, serologic testing was negative in most of the patients with viable intraretinal nematodes, which led Gass and Braunstein to suggest that Toxocara was not the causative nematode in most patients with DUSN. 4 They suggested that the nematode less than 1,000 μm in length was the dog hookworm A. caninum. Kazacos et al. later suggested that the larger nematode was the raccoon ascarid B. procyonis . 11

Retinal biopsy for DUSN via transcleral approach was performed by Blumenkranz and Culbertson. 12 However, precise identification of the nematode was not made. 13 Gass transclerally extracted one nematode from beneath the retina after killing it with cryotherapy; histologic details were poor and he was unable to identify the nematode. 14 De Souza and Nakashima recovered the nematode intact and motile via transvitreal approach. 13 Several parasitologists in São Paulo, Brazil, examined the nematode; the measurement of body size and the morphologic features were more consistent with a third stage Toxocara larva. Because of poor fixation, definitive identification of the worm was not possible, but Bowman recently reviewed the pictures of the worm removed by de Souza et al. and concluded that it is most likely A. caninum . 9 Because none of the nematodes described from patients with DUSN have been recovered intact, identification must therefore be based on a combination of careful measurement of the parasite, serologic testing, and epidemiological studies, all of which have their limitations. 15

T. canis

Gass et al. initially concluded that Toxocara was a cause of DUSN, 3 but this possibility was discarded based on negative serology in many of the reported cases. 4 In addition, Gass and Olsen later suggested that T. canis was not the cause based on the following: (1) there was a lack of serologic evidence; (2) the small size of the infective second stage larval form of T. canis made it difficult to visualize biomicroscopically; (3) the clinical picture was unlike that associated with ocular toxocariasis; and (4) the worldwide prevalence of T. canis was not in keeping with the endemic distribution of DUSN. 16 However, Goldberg et al. 15 reported that low or nondiagnostic serum titers are well described in cases of Toxocara ocular larva migrans, and suggested a similarity with the overall reduced sensitivity of serodiagnostic tests for DUSN. 17,18 Oppenheim et al. reported a case of Toxocara DUSN in which the patient’s positive enzyme-linked immunosorbent assay titer decreased fourfold over a 2-year period. 19 Therefore, the lack of serologic confirmation of toxocaral infection in some patients may be a reflection of the timing of the serology in relation to the onset of the disease or the immune status of the patient.

A. caninum

The association of cutaneous larva migrans months, several years, or immediately preceding the onset of DUSN in some patients suggests that A. caninum may be the small nematode that causes the syndrome. 9,16A. caninum is a frequent cause of cutaneous larva migrans in the southeastern United States. In addition, the infective third stage larva of A. caninum is approximately 650 μm in length and capable of surviving in host tissue, including that of humans, many months and probably years without changing size or shape. 16

B. procyonis

Kazacos et al. suggested that the larger worm in patients with DUSN living in more northern climates was B. procyonis , a nematode found in raccoons. 20 They proposed that B. procyonis larvae produce ocular larva migrans with a clinical picture similar to that of early DUSN in subhuman primates and other experimental animals after oral infection. 11 Additionally, the B. procyonis larvae may grow while they are within the eye and would account for the range of lengths of larvae seen, such as those that are 400 to 2,000 μm. The large nematode variant of DUSN matches the size range of Baylisascaris . Nevertheless, some controversy exists because most patients with DUSN have no history of exposure to raccoons 7 ; however, most patients with large nematode DUSN were from areas of the United States where raccoons are not only common, but commonly infected with B. procyonis . 21 Significant morphometric, serologic, and epidemiologic support for Baylisascaris as the causative agent of DUSN was published by Goldberg et al. 15 A large worm of 1,500 μm length presenting in a German patient was thought to be consistent with the Bayliascaris species. 22 In humans, the organism is capable of causing visceral larva migrans, eosinophilic meningoencephalitis, and ocular larva migrans. In addition, Mets et al. reported two patients with eye manifestations of DUSN, both with severe neurologic degeneration and indirect immunofluorescence assays on serum and cerebrospinal fluid positive for B. procyonis in one and serially positive and increasing in the second. 23 In addition, Goldberg et al. suggest that ocular larva migrans and DUSN can occur without evidence of visceral larva migrans or central nervous system dysfunction. 15

Trematodes

McDonald et al. encountered two cases of human intraocular infection with mesocercariae of Alaria ( Trematoda ) in the eyes of two unrelated Asian men with signs of DUSN in which the probable source of infection was ingestion of undercooked frogs’ legs containing the trematode. 24 The worm in their first case was analyzed from projected fundus photographs and diagnosed as a Alaria mesocercaria on the basis of its shape, size (500 × 150 μm), and movement. The worm in their second case was removed surgically from the vitreous and identified as A. mesocercaria , 555 × 190 μm in size, most likely Alaria americana . They concluded that A. mesocercaria could be a cause of DUSN.

Mode of Transmission

B. procyonis , a parasitic infection of raccoons in the United States, causes severe neurologic and ocular disease in humans when infectious eggs from raccoon feces are ingested. However, A. caninum , a parasitic infection of dogs (or sometimes a fox infection) in South America, causes cutaneous larva migrans in humans when infectious eggs from dog feces are ingested or when larvae entering through the skin (usually the foot) migrate through the bloodstream to the lungs and trachea and are coughed up and swallowed. They attach themselves to the intestinal wall and thus complete the life cycle.

Diagnosis and Pathogenesis

Because serologic testing has been variable, the diagnosis is made when the clinical characteristics of DUSN are found in conjunction with an intraocular worm. Clinical characteristics are manifested in early and late stages. DUSN is most frequently seen in healthy children or young adults with no significant ocular history.

Early Stage

Central or paracentral scotoma is the principal complaint of symptomatic patients in the early stage. 2 Visual loss is rarely reversible and usually less than 20/200 in approximately half of patients. 4 Patients with acute visual loss during early stages of the disease usually present mild to moderate vitritis, mild optic disc edema, and recurrent crops of evanescent, multifocal, gray-white lesions at the level of the outer retina. These lesions typically are clustered in only one segment of the fundus ( Figure 1A ). 16 Less frequently, symptoms and signs include ocular discomfort, congestion, iridocyclitis, perivenous exudation, subretinal hemorrhages, serous exudation, and evidence of subretinal neovascularization. 16

In approximately 25% to 40% of cases, a worm is visualized during eye examination. 8,25 The intraocular worm is seen as a motile, white, often glistening nematode that is gently tapered at both ends and varies in length from 400 to 2,000 μm ( Figure 1B ). It can be seen during any stage of the disease and if active gray-white lesions are present, the nematode will usually be found in their vicinity. The examining light may cause the worm to move by a series of slow coiling and uncoiling movements, and less often by slithering snake-like movements in the subretinal space. 9

Gass and Braunstein reported that there is a greater likelihood of the longer worm leaving a tract of coarse clumping of RPE in the wake of its travels. 4 The shorter worm tends to leave focal, chorioretinal atrophic scars ( Figure 2 ). The focal pigment epithelial changes seen are easily explained by the location or the travel pattern of the worm. It is speculated that focal chorioretinal white spots are an immune response to a secretion or excretion from the worm. 3 The diffuse pigment epithelial changes are somewhat more difficult to explain except as a toxic reaction. 26 The active gray-white evanescent lesions, which are probably caused by substances left by the nematode in its wake, disappear in 1 to 2 weeks as the nematode moves elsewhere in the eye. 16

There is a greater likelihood of the longer worm leaving a tract of coarse clumping of retinal pigment epithelium in the wake of its travels. The shorter worm (insert) tends to leave focal, chorioretinal atrophic scars (arrow).

Figure 2. There is a greater likelihood of the longer worm leaving a tract of coarse clumping of retinal pigment epithelium in the wake of its travels. The shorter worm (insert) tends to leave focal, chorioretinal atrophic scars (arrow).

Late Stage

The clinical picture of late stage disease usually demonstrates progressive optic atrophy with the subsequent afferent pupillary defect, mild or moderate vitritis, multifocal choroiditis episodes, increase in the internal limiting membrane reflex (Oréfice’s sign), presence of small white spots suggestive of calcifications, evidence of tunnels in the subretinal space (Garcia’s sign), retinal narrowing of the retinal arteries, marked focal and diffuse degenerative changes in the RPE and retina, and severe permanent loss of vision ( Figure 3 ). 16,27 Visual acuity in late stages is profoundly decreased, with 80% or more showing visual acuity of 20/200 or worse. 26 Over a period of weeks or months, diffuse and focal depigmentation of the RPE occurs, usually most prominent in the peripapillary and peripheral retina and less prominent in the central macular area. 9

The clinical picture of late-stage diffuse unilateral subacute neuroretinitis usually shows progressive optic atrophy, narrowing of the retinal arteries, marked focal and diffuse degenerative changes in the pigment epithelium and retina, and severe permanent loss of vision. The intraocular worm is shown in the insert.

Figure 3. The clinical picture of late-stage diffuse unilateral subacute neuroretinitis usually shows progressive optic atrophy, narrowing of the retinal arteries, marked focal and diffuse degenerative changes in the pigment epithelium and retina, and severe permanent loss of vision. The intraocular worm is shown in the insert.

Optic atrophy and severe retinal arteriole narrowing seems to define the late stage best. Retinal arteriole narrowing may vary by quadrant, and in conjunction with optic atrophy usually accompanies the progressive changes in the RPE. Choroidal neovascularization usually occurs in the periphery. 26 Although information about the pathogenesis of the disease is speculative, toxic products released by the larva in the subretinal space would locally affect the external portion of the retina and a diffuse tissue reaction would lead to external and internal retinal damage. Vascular narrowing and progressive ganglionar cell loss would occur until optic atrophy resulted. 28

Cases in which the worm is identified should be defined as confirmed DUSN, and eyes with the above-mentioned clinical features (early and late stage) but without identification of the worm should be classified as presumed DUSN. 8

Ancillary Tests

Serologic Test

Serologic testing, stool examinations, and peripheral blood smears are of little value in making the diagnosis of DUSN, 3 and no serologic test currently is available for Ancylostoma . 16 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.

Fluorescein Angiography

In the early stage, there is hypofluorescence of the focal gray-white lesions of active retinitis followed by staining. Leakage of dye is seen from the capillaries on the optic disc. Occasionally, there is evidence of prominent perivenous leakage of dye ( Figure 4 ). 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 ( Figure 5 ). 16

Serial fluorescein angiogram of a patient with early stage diffuse unilateral subacute neuroretinitis showing areas of both vascular and retinochoroidal leakage and staining.

Figure 4. Serial fluorescein angiogram of a patient with early stage diffuse unilateral subacute neuroretinitis showing areas of both vascular and retinochoroidal leakage and staining.

(A) In the early stage of diffuse unilateral subacute neuroretinitis, there is hypofluorescence of the focal gray-white lesions of active retinitis followed by staining. (B) In more advanced stages of the disease, angiography shows greater evidence of loss of pigment from the retinal pigment epithelium manifested angiographically as an irregular increase in the background choroidal fluorescence. (Photograph courtesy of Dario Fuenmayor-Rivera, MD.)

Figure 5. (A) In the early stage of diffuse unilateral subacute neuroretinitis, there is hypofluorescence of the focal gray-white lesions of active retinitis followed by staining. (B) In more advanced stages of the disease, angiography shows greater evidence of loss of pigment from the retinal pigment epithelium manifested angiographically as an irregular increase in the background choroidal fluorescence. (Photograph courtesy of Dario Fuenmayor-Rivera, MD.)

Indocyanine Green (ICG) Angiography

ICG angiography features suggest that the choroid is also involved in early stage DUSN. Choroidal infiltration, which prevents normal choroidal ICG impregnation, is most likely the physiopathogenic explanation for the hypofluorescent dark spots seen in the affected eye. The dark spots, present in the initial ICG angiography 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, whereas dots becoming isofluorescent in the late phase are interpreted as partial-thickness lesions progressively surrounded by ICG fluorescence ( Figure 6 ). 29

Early stage diffuse unilateral subacute neuroretinitis. (A) The affected eye revealed multiple yellow-white subretinal lesions at the posterior pole. (B) Early phase indocyanine green angiography shows hypofluorescence of the lesions. (C) Late phase indocyanine green angiography reveals few hypofluorescent dots and a fuzzy hyperfluorescence in the macular region. (D) After 1 month, the superior subretinal lesions increased in number and became more evident. (Reprinted with permission from Vianna RN, Onofre G, Ecard V, Muralha L, Muralha A, de A Garcia CA. Indocyanine green angiography in diffuse unilateral subacute neuroretinitis. Eye (Lond). 2006;20:1113–1116.)

Figure 6. Early stage diffuse unilateral subacute neuroretinitis. (A) The affected eye revealed multiple yellow-white subretinal lesions at the posterior pole. (B) Early phase indocyanine green angiography shows hypofluorescence of the lesions. (C) Late phase indocyanine green angiography reveals few hypofluorescent dots and a fuzzy hyperfluorescence in the macular region. (D) After 1 month, the superior subretinal lesions increased in number and became more evident. (Reprinted with permission from Vianna RN, Onofre G, Ecard V, Muralha L, Muralha A, de A Garcia CA. Indocyanine green angiography in diffuse unilateral subacute neuroretinitis. Eye (Lond) . 2006;20:1113–1116.)

Electroretinogram, Electro-oculogram, and Multifocal Electroretingram

Electroretinographic changes include a mild to moderate decrease in rod and cone function, with the b-wave being more affected than the a-wave. DUSN presents a characteristic and reproducible electroretinographic picture also found in ischemic retinal cases: negative electroretinogram (b-wave of maximum combined response is flat, with below normal response and a decrease in relation to b/a). The mechanism of this interesting phenomenon is explained as being a consequence of a possible autoimmune, inflammatory, and/or toxic aggression toward retinal bipolar cells. 27,28 The electroretinogram (ERG) in the affected eye is usually abnormal even if tested early in the course of the disease. The more common one-half of patients can have a normal electrooculogram and the finding of normal electrooculogram and abnormal ERG suggests a neuroepithelium disease. 25 It is important that the ERG is rarely extinguished completely, which differentiates it from some tapetoretinal degeneration. 30 According to Martidis et al., multifocal ERG findings before laser treatment showed decreased foveal response density and increased parafoveal and perifoveal waveform amplitudes. Two months after laser photocoagulation of a subretinal nematode, multifocal ERG showed full recovery of normal findings and visual acuity remained 20/20. 31

Visual Field Studies

Visual fields show different lesion patterns that cannot be explained with the findings of the ocular fundus changes. 16 Goldmann perimetry is useful to evaluate the remaining visual field before and after treatment of the disease ( Figure 7 ). 30

Visual field demonstrates different lesion patterns that cannot be explained with the findings of the ocular fundus changes. Goldmann perimetry is useful to evaluate remaining visual field before and after treatment of diffuse unilateral subacute neuroretinitis. (Photograph courtesy of Eduardo Cunha de Souza, MD.)

Figure 7. Visual field demonstrates different lesion patterns that cannot be explained with the findings of the ocular fundus changes. Goldmann perimetry is useful to evaluate remaining visual field before and after treatment of diffuse unilateral subacute neuroretinitis. (Photograph courtesy of Eduardo Cunha de Souza, MD.)

Scanning Laser Ophthalmoscopy

Examination with scanning laser ophthalmoscopy provides a high-contrast image that may facilitate visualization of the nematode. Live video imaging with the scanning laser ophthalmoscopy may also help document motility. 32

Optical Coherence Tomography

Statistical analysis with Stratus optical coherence tomography (Carl Zeiss Meditec, Inc., Dublin, CA) showed there was no significant difference between the retinal nerve fiber layer (RNFL) thickness in patients with or without live worm. However, there was statistical significance between decreased RNFL thickness and worse visual acuity ( Figure 8 ). 33

Late-stage diffuse unilateral subacute neuroretinitis. (A) Color fundus image of a 12-year-old boy with a 6-month history of visual loss. Visual acuity was 20/400. Optic nerve atrophy, retinal vessel narrowing, and some degree of pigmentary changes can be visualized. (B) High-resolution B-scan optical coherence tomography (OCT) through the fovea showing a thinning in the inner retinal layers. (C–D) OCT retinal thickness map (Cirrus; Carl Zeiss Meditec, Inc., Dublin, CA) showing a diffuse retinal thinning. (E–F) OCT fundus image and retinal nerve fiber layer map displaying a reduced retinal nerve fiber layer thickness.

Figure 8. Late-stage diffuse unilateral subacute neuroretinitis. (A) Color fundus image of a 12-year-old boy with a 6-month history of visual loss. Visual acuity was 20/400. Optic nerve atrophy, retinal vessel narrowing, and some degree of pigmentary changes can be visualized. (B) High-resolution B-scan optical coherence tomography (OCT) through the fovea showing a thinning in the inner retinal layers. (C–D) OCT retinal thickness map (Cirrus; Carl Zeiss Meditec, Inc., Dublin, CA) showing a diffuse retinal thinning. (E–F) OCT fundus image and retinal nerve fiber layer map displaying a reduced retinal nerve fiber layer thickness.

GDx Nerve Fiber Analyzer

The GDx Nerve Fiber Analyzer (Carl Zeiss Meditec, Inc.) is a scanning confocal laser polarimeter that uses a polarized light source to analyze the RNFL around the optic nerve. According to Garcia et al., it is possible to have two types of RNFL alterations: (1) increase in thickness due to transitory edema or (2) decrease in thickness secondary to nerve fiber loss that occurs with the progression of the disease. They concluded that the GDx Nerve Fiber Analyzer was able to demonstrate a decrease in RNFL thickness during the chronic phase. This is important for patients whose larva was not found and who underwent only clinical treatment, so that the progression of the disease may be monitored. 27

Differential Diagnosis

Early signs of DUSN often are mistaken for sarcoid 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 posttraumatic chorioretinopathy, occlusive vascular disease, sarcoid, or toxic retinopathy. 16

Management

Laser Treatment

Currently, 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. The authors’ current technique includes the use of a 532-nm green laser (EYELITE Laser; Alcon Laboratories, Inc., Fort Worth, TX), with a 200-μm spot size, at a power of 200 mW (whiting), using confluent direct laser, with an average of 4 to 5 spots ( Figure 9 ). Some improvement in vision and visual field may occur after laser treatment of the worm. 34 However, in late stages of the disease, laser treatment does not improve the visual acuity of affected patients. 35 Previous studies have demonstrated the photosensitivity of different species of ocular infecting parasites and this may be used in luring the target organism away from the macula. In some patients where the worm is close to the center of the fovea and heavy photocoagulation may damage the remaining central vision, it may be possible to use low level illumination or light applications of the laser to chase the worm into the midperiphery, where it may be destroyed with less retinal damage. 36 In addition, laser treatment should be performed as soon as the worm is identified, because they are motile and may be difficult to locate if the procedure is delayed. 37

(A–B) Laser photocoagulation technique of the worm includes the use of a 532-nm green laser, with a 200-μm spot size, at a power of 200 mW (whiting), using confluent direct laser, with an average of 4 to 5 spots. The illustration demonstrates a worm (A, yellow circle) along the inferotemporal vascular arcade in the right eye (B) photocoagulated with such parameters.

Figure 9. (A–B) Laser photocoagulation technique of the worm includes the use of a 532-nm green laser, with a 200-μm spot size, at a power of 200 mW (whiting), using confluent direct laser, with an average of 4 to 5 spots. The illustration demonstrates a worm (A, yellow circle) along the inferotemporal vascular arcade in the right eye (B) photocoagulated with such parameters.

Oral Treatment

Thiabendazole and corticosteroids have not usually been successful for the treatment of DUSN, except in patients with vitreous inflammation. Gass and Olsen reported that thiabendazole could be effective in some patients when the worm cannot be found and when DUSN is accompanied by moderate degrees of vitreous inflammation associated with a breakdown in the blood–retinal barrier. 16 Similarly, in this group of patients without visible worm and the typical migration of the evanescent lesions, Gass and Olsen proposed the use of moderately intense scatter photocoagulation in the vicinity of the white lesions to break down the blood–retinal barrier before the administration of thiabendazole. Observation of new white retinal lesions 4 to 7 days after treatment may indicate death of the nematode. Souza et al. described 12 Brazilian patients who improved visual acuity, visual field, and active ocular inflammatory signs after treatment exclusively with high-dose oral albendazole (400 mg/d) for 30 days. 38 In addition, during the first weeks of treatment, they observed worm inactivation in four patients in whom the worms were visible. No adverse drug side effects were observed in any of their cases during follow-up examination.

Pars Plana Vitrectomy

Pars plana vitrectomy is not the standard of treatment for DUSN when the nematode is found because it can be eradicated in cooperative patients with laser treatment. However, as previously stated, de Souza et al. recovered the nematode intact with a pars plana vitrectomy approach and in an uncooperative young patient with standard laser treatment. 13 In addition, Meyer-Riemann et al. demonstrated that when a nematode larva is near the posterior pole, surgical extraction of the worm using vitrectomy techniques may be favorable compared to photocoagulation. 39

Discussion

DUSN is usually a unilateral inflammatory disease characterized by an insidious, usually severe loss of peripheral and central vision with associated findings of vitreous inflammation, diffuse and focal epithelial derangement with relative sparing of the macula, narrowing of the retinal vessels, optic atrophy, increased retinal circulation time, and subnormal electroretinographic findings. Parasites of different sizes and several species of nematodes have been reported as the etiologic agent of DUSN, including T. canis , B. procyonis , and A. caninum , and most of these reports do not present conclusive evidence about the specific agent. Clinical characteristics are manifested in early and late stages but pathogenesis of the disease is speculative, including autoimmune, inflammatory, and/or toxic mechanism of aggression as a possible cause of retinal damage. Laser photocoagulation offers the best chance for clinical resolution of the disease, but the worm is visualized during eye examination in only 25% to 40% of cases. In those patients who cannot receive laser treatment, other treatments including pars plana vitrectomy, thiabendazole, and albendazole have been used with variable success. Currently, the best protocol option for oral treatment is albendazole; however, the optimal dose and duration of treatment for DUSN has still not been determined and the suggestion to use 400 mg for 30 consecutive days is on the basis of the good results observed applying this protocol to patients with neurocysticercosis. 38

References

  1. Gass JD. Subretinal migration of a nematode in a patient with diffuse unilateral subacute neuroretinitis. Arch Ophthalmol . 1996;114:1526–1527. doi:10.1001/archopht.1996.01100140724018 [CrossRef]
  2. Gass JD, Scelfo R. Diffuse unilateral subacute neuroretinitis. J R Soc Med . 1978;71:95–111.
  3. Gass JD, Gilbert WR Jr, Guerry RK, Scelfo R. Diffuse unilateral subacute neuroretinitis. Ophthalmology . 1978;85:521–545. doi:10.1067/mpa.2000.106963 [CrossRef]
  4. Gass JD, Braunstein RA. Further observations concerning the diffuse unilateral subacute neuroretinitis syndrome. Arch Ophthalmol . 1983;101:1689–1697. doi:10.1001/archopht.1983.01040020691004 [CrossRef]
  5. Parsons HE. Nematode chorioretinitis: report of a case, with photographs of a viable worm. AMA Arch Ophthalmol . 1952;47:799–800. doi:10.1001/archopht.1952.01700030818011 [CrossRef]
  6. Nussenblatt RB. Onchocercasis and other parasitic diseases. In: Nussenblatt RB, Whitcup SM, eds. Uveitis: Fundamentals and Clinical Practice ; 3rd ed. St. Louis, MO: Mosby; 2004:250–263. doi:10.1016/j.ajo.2006.02.030 [CrossRef]
  7. de Souza EC, Abujamra S, Nakashima Y, Gass JD. Diffuse bilateral subacute neuroretinitis: first patient with documented nematodes in both eyes. Arch Ophthalmol . 1999;117:1349–1351. doi:10.1001/archopht.117.10.1349 [CrossRef]
  8. de Amorim Garcia Filho CA, Gomes AH, de A Garcia Soares AC, de Amorim Garcia CA. Clinical features of 121 patients with diffuse unilateral subacute neuroretinitis. Am J Ophthalmol . 2012;153:743–749. doi:10.1016/j.ajo.2011.09.015 [CrossRef]
  9. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment (Vol. 2) , 3rd ed. St. Louis, MO: Mosby; 1987:622–628. doi:10.1016/j.ophtha.2009.03.013 [CrossRef]
  10. Moraes LR, Cialdini AP, Avila MP, Elsner AE. Identifying live nematodes in diffuse unilateral subacute neuroretinitis by using the scanning laser ophthalmoscope. Arch Ophthalmol . 2002;120:135–138. doi:10.1001/archopht.120.2.135 [CrossRef]
  11. Kazacos KR, Raymond LA, Kazacos EA, Vestre WA. The raccoon ascarid: a probable cause of human ocular larva migrans. Ophthalmology . 1985;92:1735–1744. doi:10.1136/bjo.2010.195081 [CrossRef]
  12. Blumenkranz MS, Culberston WW. Chorioretinal biopsy: description of a technique. In: Ryan SJ, Dawson AK, Little HL, eds. Retinal Diseases . Orlando, FL: Grune & Stratton; 1985:46. doi:10.1167/iovs.10-5550 [CrossRef]
  13. de Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis: report of transvitreal surgical removal of a subretinal nematode. Ophthalmology . 1995;102:1183–1186. doi:10.1167/iovs.06-0426 [CrossRef]
  14. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. (Vol.2) , 3rd ed. St. Louis, MO: Mosby; 1987:470–475.
  15. Goldberg MA, Kazacos KR, Boyce WM, Ai E, Katz B. Diffuse unilateral subacute neuroretinitis: morphometric, serologic, and epidemiologic support for Baylisascaris as a causative agent. Ophthalmology . 1993;100:1695–1701. doi:10.1016/j.jfo.2009.06.002 [CrossRef]
  16. Gass JDM, Olsen KR. Diffuse unilateral subacute neuroretinitis. In: Ryan SJ, Schachat AP, eds. Retina , 3rd ed. St. Louis, MO: Mosby; 2001:1669–1678. doi:10.3928/01913913-20091019-06 [CrossRef]
  17. Searl SS, Moazed K, Albert DM, Marcus LC. Ocular toxocariasis presenting as leukocoria in a patient with low ELISA titer to Toxocara canis. Ophthalmology . 1981;88:1302–1306.
  18. Wilson M, Schantz P. Nonmorphologic diagnosis of parasitic infections. In: Balows A, ed. Manual of Clinical Microbiology , 5th ed. Washington, DC: American Society for Microbiology; 1991;67:723. doi:10.2147/OPTH.S13145 [CrossRef]
  19. Oppenheim S, Rogell G, Peyser R. Diffuse unilateral subacute neuroretinitis. Ann Ophthalmol . 1985;17:336–338. doi:10.3341/kjo.2006.20.3.177 [CrossRef]
  20. Kazacos KR, Vestre WA, Kazacos EA, Raymond LA. Diffuse unilateral subacute neuroretinitis syndrome: probable cause. Arch Ophthalmol . 1984;102:967–968. doi:10.1001/archopht.1984.01040030775008 [CrossRef]
  21. Kazacos KR, Boyce WM. Baylisascaris larva migrans. J Am Vet Med Assoc . 1989;195:894–903. doi:10.1016/j.ophtha.2006.01.036 [CrossRef]
  22. Küchle M, Knorr HL, Medenblik-Frysch S, Weber A, Bauer C, Naumann GO. Diffuse unilateral subacute neuroretinitis syndrome in a German most likely caused by the raccoon roundworm, Baylisascaris procyonis. Graefes Arch Clin Exp Ophthalmol . 1993;231:48–51. doi:10.1007/BF01681701 [CrossRef]
  23. Mets MB, Noble AG, Basti S, et al. Eye findings of diffuse unilateral subacute neuroretinitis and multiple choroidal infiltrates associated with neural larva migrans due to Baylisascaris procyonis. Am J Ophthalmol . 2003;135:888–890. doi:10.1016/S0002-9394(02)01539-8 [CrossRef]
  24. McDonald HR, Kazacos KR, Schatz H, Johnson RN. Two cases of intraocular infection with Alaria mesocercaria (Trematoda) Am J Ophthalmol . 1994;117:447–455.
  25. Stokkermans TJ. Diffuse unilateral subacute neuroretinitis. Optom Vis Sci . 1999;76:444–454. doi:10.1097/00006324-199907000-00019 [CrossRef]
  26. Barney NP. Diffuse unilateral subacute neuroretinitis. In: Foster CS, Vitale AT, eds. Diagnosis and Treatment of Uveitis , 1st ed. Philadelphia: W.B. Saunders; 2002:475–479.
  27. Garcia CA, de Oliveira AG, de Lima CE, Rocha FN, Garcia Filho CA. Retinal nerve fiber layer analysis using GDx in 49 patients with chronic phase DUSN. Arq Bras Oftalmol . 2006;69:631–635. doi:10.1590/S0004-27492006000500002 [CrossRef]
  28. Oréfice F, Bonfioli AA, Paranhos FRL. Diffuse unilateral subacute neuroretinitis. In: Oréfice F, ed. Uveitis: Clinical and Surgical . Rio de Janeiro, Brazil: Cultura Médica; 1998:733–756.
  29. Vianna RN, Onofre G, Ecard V, Muralha L, Muralha A, de A Garcia CA. Indocyanine green angiography in diffuse unilateral subacute neuroretinitis. Eye (Lond) . 2006;20:1113–1116. doi:10.1038/sj.eye.6702154 [CrossRef]
  30. Sabrosa NA, de Souza EC. Nematode infections of the eye: toxocariasis and diffuse unilateral subacute neuroretinitis. Curr Opin Ophthalmol . 2001;12:450–454. doi:10.1097/00055735-200112000-00010 [CrossRef]
  31. Martidis A, Greenberg PB, Rogers AH, Velázquez-Estades LJ, Baumal CR. Multifocal electroretinography response after laser photocoagulation of a subretinal nematode. Am J Ophthalmol . 2002;133:417–419. doi:10.1016/S0002-9394(01)01331-9 [CrossRef]
  32. Moraes LR, Cialdini AP, Avila MP, Elsner AE. Identifying live nematodes in diffuse unilateral subacute neuroretinitis by using the scanning laser ophthalmoscope. Arch Ophthalmol . 2002;120:135–138. doi:10.1001/archopht.120.2.135 [CrossRef]
  33. Gomes AH, Garcia CA, Segundo Pde S, Garcia Filho CA, Garcia AC. Optic coherence tomography in a patient with diffuse unilateral subacute neuroretinitis. Arq Bras Oftalmol . 2009;72:185–188. doi:10.1590/S0004-27492009000200010 [CrossRef]
  34. Garcia CA, Gomes AH, Garcia Filho CA, Vianna RN. Early-stage diffuse unilateral subacute neuroretinitis: improvement of vision after photocoagulation of the worm. Eye (Lond) . 2004;18:624–627. doi:10.1038/sj.eye.6700742 [CrossRef]
  35. Garcia CA, Gomes AH, Vianna RN, Souza Filho CA, Oréfice F. Late-stage diffuse unilateral subacute neuroretinitis: photocoagulation of the worm does not improve the visual acuity of affected patients. Int Ophthalmol . 2005;26:39–42. doi:10.1007/s10792-005-0078-8 [CrossRef]
  36. McDonald HR. Diagnostic and therapeutic challenges: diffuse unilateral subacute neuroretinitis. Retina . 2003;23:92–96. doi:10.1097/00006982-200302000-00015 [CrossRef]
  37. Venkatesh P, Sarkar S, Garg S. Diffuse unilateral subacute neuroretinitis: report of a case from the Indian subcontinent and the importance of immediate photocoagulation. Int Ophthalmol . 2005;26:251–254. doi:10.1007/s10792-007-9045-x [CrossRef]
  38. Souza EC, Casella AM, Nakashima Y, Monteiro ML. Clinical features and outcomes of patients with diffuse unilateral subacute neuroretinitis treated with oral albendazole. Am J Ophthalmol . 2005;140:437–445. doi:10.1016/j.ajo.2005.03.065 [CrossRef]
  39. Meyer-Riemann W, Petersen J, Vogel M. An attempt to extract an intraretinal nematode located in the papillomacular bundle [article in German]. Klin Monatsbl Augenheilkd . 1999;214:116–119. doi:10.1055/s-2008-1034761 [CrossRef]

10.3928/01913913-20121211-03

Sign up to receive

Journal E-contents