Unilateral Subacute Neuroretinitis (DUSN)


Fig. 25.1

(a, b) Fundus photographs demonstrating early stage findings of DUSN. There are crops evanescent, multifocal, gray-white lesions at the level of the outer retina in the superior fundus (arrow). The intraocular worm is seen in insert (b) as a motile, white worm



This chapter reviews the pathogenesis, clinical features, differential diagnoses, and management options for diffuse unilateral subacute neuroretinitis.


Etiology and Mode of Transmission


Various parasites and nematodes have been reported as the etiologic agent of DUSN; however, most of these reports did not provide conclusive evidence (Arevalo et al. 2013). The smaller nematodes measuring 400–700 μm in size include Toxocara canis and Ancylostoma caninum were seen more commonly than the larger ones ranging from 1000 to 2000 μm in length, corresponding to Baylisascaris procyonis (Gass 1987). Rarely, Thelazia, nematodes of 4500–17,000 μm in size, were implicated in DUSN (Gass and Scelfo 1978; Kunavisarut et al. 2014). The smaller nematodes are endemic to the southeastern United States, the Caribbean islands, and South America, whereas the larger nematodes are found in the Midwestern United States. Trematodes, flatworms, have also been reported in DUSN.


Identification of the causative nematode in DUSN has been challenging as few were surgically extracted from the eye, and fewer were recovered intact (Arevalo et al. 2013). Blumenkranz and Culbertton performed a retinal biopsy via a transcleral approach but could not identify the organism (Blumenkranz and Culbertton 1985). Gass extracted a subretinal nematode transclerally after applying cryotherapy, although he could not identify the organism due to poor histologic details (Gass 1987). Therefore, traditionally, identification of the organism has been based on a combination of examination of morphologic features, serologic testing, and epidemiologic studies. More recently, newer techniques allow for the identification of nematodes through molecular studies and phylogenetic analyses (Poppert et al. 2017; Liu 2012). Polymerase chain reaction amplification and sequencing analysis of ribosomal ribonucleic acid and internal transcribed spacer regions 1 and 2 are used as target regions to differentiate between various parasites (Liu 2012). In the future, perhaps these techniques can be applied to intraocular fluid samples to help the identification of nematodes.


Toxocara canis


Toxocara is an infection in canine hosts accounting for the most prevalent human helminthic infection in industrialized countries (Hotez and Wilkins 2009). Humans acquire the disease via contaminated water sources and ingestion of infected raw meat. Gass initially hypothesized that Toxocara was a cause of DUSN (Gass et al. 1978), however ruled out this possibility based on negative serology in many patients. Additionally, the small size of the larval stage of Toxocara made it difficult to be seen biomicroscopically (Gass and Braunstein 1983). It is poorly understood why the clinical picture is different from that associated with ocular toxocariasis. Goldberg et al. described cases with evidence that low or nondiagnostic serum titers can be found in cases of Toxocara ocular larva migrans and may represent a false-negative test result (Goldberg et al. 1993; Searl et al. 1981; Wilson and Schantz 1991). Oppenheim et al. reported a case of Toxocara DUSN in which the patient’s positive ELISA titer decreased fourfold over a 2-year period (Oppenheim et al. 1985). Therefore, a negative serologic test may be related to the timing of the serology in relation to the onset of the disease or the immune status of the patient.


Ancylostoma caninum


This worm is a parasitic infection of dogs in South America. Ancylostoma ceylanicum has been reported in dogs and cats in Southeast Asia, India, and Australia (Carroll and Grove 1986). A. caninum is a frequent cause of cutaneous larva migrans in the southeastern United States. Cutaneous larva migrans can be acquired through the fecal–oral route with dog feces contaminated with infectious eggs. Alternatively, larvae may enter through the skin, migrate through the blood stream to the lungs and trachea, and are then coughed up and swallowed into the gastrointestinal system. They attach themselves to the intestinal wall and begin to reproduce. Once eggs are shed into the environment through feces, the life cycle is complete (Arevalo et al. 2013).


In earlier reports, Gass and Braunstein suggested that the nematode less than 1000 μm in length was the dog hookworm, Ancylostoma caninum (Gass and Braunstein 1983). Later, de Souza et al. recovered an intact and motile organism via transvitreal approach (de Souza and Nakashima 1995). While parasitologists believed that morphologic features were consistent with a third-stage Toxocara larva, a photograph review by Bowman concluded that it was most likely A. caninum (Gass 1987). The association of cutaneous larva migrans months, several years, or immediately preceding the onset of DUSN in some patients suggests that Ancylostoma caninum may be the small nematode that causes the syndrome (Gass 1987; Gass and Olsen 2001). In addition, the infective third larval stage of A. caninum is capable of surviving in host tissue for years without changing size or shape (Gass and Olsen 2001). In one case reported by Poppert et al., although the worm was destroyed during surgical extraction, it was identified through DNA sequencing and phylogenetic analysis of intraoperative fluids as A. ceylanicum (Poppert et al. 2017).


Baylisascaris procyonis


Baylisascaris procyonis is a nematode causing a parasitic infection of raccoons. In humans, it causes severe neurologic and ocular diseases, including visceral larva migrans, ocular larva migrans, and eosinophilic meningoencephalitis (Fox et al. 1985; Mets et al. 2003). B. procyonis can be detected in the serum and cerebrospinal fluid using indirect immunofluorescence assays. Goldberg reported ocular larva migrans and DUSN occurring without systemic evidence of infection (Goldberg et al. 1993).


In 1984, Kazacos suggested that the larger worm in patients with DUSN living in more northern climates was Baylisascaris procyonis (Kazacos et al. 1984). He proposed that B. procyonis larvae produce ocular larva migrans with a clinical picture that is similar to that of early DUSN in subhuman primates and other experimental animals after oral infection (Kazacos et al. 1985). Additionally, the B. procyonis larvae may grow while in the eye and can account for the range of lengths of larvae seen (400–2000 μm), matching the larger nematode variant of DUSN (Kuchle et al. 1993). Although most patients have no history of raccoon exposure, most patients with large nematode DUSN are from the areas of the United States with raccoons commonly infected with B. procyonis (de Souza et al. 1999; Kazacos and Boyce 1989). Furthermore, large nematode DUSN occurred in the same regions where animal and human diseases due to B. procyonis have been recorded (midwestern and northeastern regions of the United States). Environmental contamination with raccoon fecal materials is common around suburban homes and barns. Accidental hand-to-mouth transfer of infective B. procyonis eggs may cause infection in humans (Goldberg et al. 1993).


Trematodes


Four cases of intraocular trematodes have been reported in the literature in association with DUSN (McDonald et al. 1994; Shea et al. 1973; Schweitzer et al. 2008). All of them were identified based on shape, size, and movement. McDonald et al. encountered two cases of human intraocular infection with Alaria mesocercariae in which the probable source of infection was ingestion of undercooked frog legs containing the trematode (McDonald et al. 1994). The worm in the first case was analyzed from fundus photographs, whereas in the second case, it was removed surgically from the vitreous cavity.


Clinical Features and Pathogenesis


Clinical characteristics can be classified into early and late stages. DUSN is most frequently seen in healthy children or young adults with no significant past ocular history. In the largest series of patients with DUSN described by de Amorim Garcia Filho et al., 69.4% of 121 patients were younger than 20 years of age (de Amorim Garcia Filho et al. 2012). Most patients presented in the late stage (92.6%) compared to 7.4% of patients presenting in the early stage. DUSN manifests as an intraocular inflammatory process characterized by multifocal chorioretinal lesions. The most common clinical features were subretinal tracks (91.7%), focal alterations of the RPE (89.3%), small white spots (80.2%), and optic nerve atrophy (76.9%). The pathogenesis of DUSN is believed to be a result of a local toxic effect on the outer retina caused by the worm, as well as a diffuse reaction in the inner and outer retina due to a toxin (Gass and Braunstein 1983; Arevalo et al. 2013b). Early and late stage findings outlined below correspond to an inflammatory reaction to the worm and its secreted toxins.


Early Stage


The chief complaint in symptomatic patients in the early stages is the presence of a central or paracentral scotoma (Gass and Scelfo 1978). Visual loss is severe at 20/200 to 20/400 or less in more than half of the patients and is usually irreversible (Gass and Braunstein 1983; de Amorim Garcia Filho et al. 2012). Patients with acute visual loss during early stages of the disease usually present with mild to moderate vitritis, mild optic disc edema, and recurrent evanescent, multifocal, gray-white lesions at the level of the outer retina. These lesions are typically clustered in only one segment of the fundus and fade within 7–10 days (Gass and Olsen 2001) (Fig. 25.1a). Less common clinical features include ocular discomfort, congestion, iridocyclitis, perivenous exudation, subretinal hemorrhages, serous exudation, and evidence of subretinal neovascularization (Gass and Olsen 2001). In approximately 25–40% of cases, a worm is visualized during the eye examination, and the most common location was in the posterior pole (17.3%) (Amorim et al. 2012; Stokkermans 1999). The intraocular worm is observed as a motile, white, glistening nematode that is tapered at both ends and varies in length from 400 to 2000 μm (Fig. 25.1b). It can be seen during any stage of the disease and often near the edges of active gray-white lesions. The worm can assume a coiled, S-shape, or figure of “8” configuration. 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 (Gass 1987). Identification of the nematode was associated with younger age, the presence of multifocal yellow-white lesions, and vitritis (de Amorim Garcia Filho et al. 2012). The focal pigment epithelial changes can be explained by the location or the travel pattern of the worm. The longer worm has a greater likelihood of leaving a tract of coarse clumping of RPE in the wake of its travels, whereas the shorter worm tends to leave focal, chorioretinal atrophic scars (Fig. 25.2) (Gass and Braunstein 1983). Focal chorioretinal white spots are thought to be an immune response to a secretion or excretion from the worm (Gass et al. 1978). The diffuse pigment epithelial changes are believed to be a toxic reaction (Barney 2002). The active gray-white evanescent lesions, which may be caused by substances left by the nematode in its wake, disappear in 1–2 weeks as the nematode travels elsewhere in the eye (Gass and Olsen 2001).

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Fig. 25.2

The nematode (seen in the insert) may leave focal atrophic chorioretinal scars (arrow)


Late Stage


Visual acuity in late stages is profoundly decreased, with 80% or more showing vision 20/200 or worse (Barney 2002). The clinical picture of late stage disease is characterized by progressive optic atrophy and diffuse RPE changes in the peripapillary and peripheral retina over a period of weeks to months (Gass 1987; Arevalo et al. 2013b). Other signs which may be seen in DUSN includes afferent pupillary defect, mild or moderate vitritis, multifocal choroidal lesions, 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), and narrowing of the retinal arteries (Fig. 25.3) (Garcia et al. 2006; Gass and Olsen 2001). Retinal arteriole narrowing may vary by quadrant, and progressive ganglion cell loss leads to optic atrophy (Oréfice et al. 1998). Rarely, choroidal neovascularization can occur in the periphery in the late stage (Barney 2002).

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Fig. 25.3

This fundus photograph demonstrates the late stage of the disease with optic nerve pallor, narrowing of the retinal arteries, and focal as well as diffuse degenerative changes in the retina and retinal pigment epithelium. The intraocular worm is shown in the insert


Diagnostic Testing


The diagnosis of DUSN is clinical and depends on the ability to identify a worm in the retina (Arevalo et al. 2013). These cases are defined as confirmed DUSN. Eyes with early and late stage clinical features consistent with DUSN, but without identification of the worm, should be classified as presumed DUSN (de Amorim Garcia Filho et al. 2012). The diagnostic tests described below are nonspecific for the diagnosis of DUSN. The advent of phylogenetic analysis of ocular fluids may become useful in the future as a diagnostic tool in identifying the parasite.


Serology


Serologic testing, stool examinations, and peripheral blood smears are of little value in making the diagnosis of DUSN (Gass et al. 1978). Moreover, no serologic test exists for Ancylostoma (Gass and Olsen 2001). When a worm is identified in the eye of an otherwise healthy person, unless a peripheral eosinophilia is present, no further evaluation seems warranted to make the diagnosis.


Diagnostic Imaging


Fluorescein angiography: DUSN is characterized by early hypofluorescence of the focal gray-white lesions of active retinitis followed by late staining. There may be disc leakage as well as prominent perivenous leakage (Fig. 25.4). In more advanced stages of the disease, fluorescein angiography shows increased background choroidal fluorescence due to progressively increased loss of RPE (Fig. 25.5) (Gass and Olsen 2001). These findings are nonspecific and may be found in other chorioretinal diseases.

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Fig. 25.4

Fluorescein angiogram performed on a patient with early stage DUSN showing areas of late leakage and staining and perivenous leakage inferiorly


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Fig. 25.5

(a) In the early stage, fluorescein angiography shows early hypofluorescence of the focal gray-white lesions of active retinitis with late staining. (b) In more advanced stages of the disease, angiography shows greater evidence of loss of pigment from the RPE and hyperfluorescence


Indocyanine green angiography (ICG-A): ICG-A demonstrates early hypofluorescent dark spots in DUSN. In the late phase, some lesions are persistently hypofluorescent and others become isofluorescent. These lesions suggest choroidal infiltration in DUSN, and late phase fluorescence may be related to degree of choroidal involvement. Persistently hypofluorescent dots are thought to be full-thickness lesions not allowing ICG to diffuse, whereas isofluorescent dots are likely partial-thickness lesions (Fig. 25.6) (Vianna et al. 2006).

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Mar 22, 2020 | Posted by in OPHTHALMOLOGY | Comments Off on Unilateral Subacute Neuroretinitis (DUSN)

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