J. Michael Jumper,
H. Richard McDonald,
Robert N. Johnson,
Arthur D. Fu,
Everett Ai
INTRODUCTION
As he did with many other retinal inflammatory diseases, J Donald M Gass meticulously investigated and described the condition he would eventually name diffuse unilateral sub-acute neuroretinitis (DUSN). For 15 years prior to the groundbreaking paper in 1978, he and his colleagues had recognized a "unilateral retinal wipe-out syndrome" in which healthy young individuals developed: "(1) insidious, usually severe loss of peripheral and central vision; (2) vitritis; (3) diffuse and focal pigment epithelial derangement with relative sparing of the macula; (4) narrowing of the retinal vessels; (5) optic atrophy; (6) increased retinal circulation time; and (7) subnormal electroretinographic findings."[1] Further observation led to the discovery of the earlier findings including: "mild optic nerve head edema, multifocal areas of active chorioretinitis and occasionally, iridocyclitis."[1] Later that year, Dr Gass and colleagues described 12 additional cases of DUSN, two in whom a motile subretinal nematode was observed.[2] Over the next 5 years, he further studied his and other reported cases[3-6] which led to the hypothesis that at:
|
(1) |
at least two different nematodes can cause this syndrome |
|
|
(2) |
there are endemic geographic regions for the different sized nematodes and |
|
|
(3) |
laser photocoagulation of the worm can halt disease progression.[7] |
In the nearly three decades since the original description, dozens of papers have been written to identify the likely pathogens, report cases in other regions of the world and describe the findings of newer diagnostic tests performed on patients with DUSN. However, the observations of Dr Gass and his colleagues have withstood the test of time.
EPIDEMIOLOGY
There have been over 200 cases of DUSN published in the literature to date, in the form of six case series each containing 4-78 patients with the rest being case reports of one to three patients (Table 167.1). DUSN is a rare condition and incidence data is not available. It has been described to occur in the Southeast,[2,6] upper Midwest,[5,8] Northeast[9,10] and Northwest[11,12] United States. Other countries with reported cases include Canada,[13] France,[14] Scotland,[15] Switzerland,[16] Germany,[17,18] Senegal,[19] Liberia,[20] India,[21] and China.[22] de Souza and coworkers from Brazil were the first to report cases outside of the United States or Caribbean Islands.[23] Recently, large series have been published from Venezuela and Brazil.[24-26]
TABLE 167.1 -- Meta-Analysis of Diffuse Unilateral Subacute Neuroretinitis
|
Author |
No. of Patients (No. of Eyes) |
M:F Ratio |
Average Age (Range) |
Worm Identified |
|
Gass et al[2] |
37 (38) |
22:15 |
16 (8-41) |
2/38 |
|
Gass and Braunstein[7] |
10 |
6:4 |
25.5 (13-65) |
10/10 |
|
Gass et al[45] |
4 |
2:2 |
10.5 (4-16) |
1/4 |
|
Cortez et al[24] |
78 (82) |
45:33 |
16.7 (7-64) |
33/82 |
|
Souza et al[25] |
12 |
8:4 |
15.4 (7-36) |
4/12 |
|
de Garcia et al[26] |
22 |
12:10 |
15.6 (5-37) |
22/22 |
|
Garcia et al[43] |
4 |
4:0 |
14.2 (9-23) |
4/4 |
|
Case reports[*] |
42 (44) |
26:16 |
23.9 (2-84) |
38/44 |
|
Total |
209 (216) |
125:84 |
17.5 years (2-84) |
114/216 (52%) |
|
* |
References 3-6, 8-13, 16, 17, 19, 20, 22, 23, 27, 28, 30-32, 35, 37, 38, 42, 44, 46-49. |
Meta-analysis of the peer-reviewed literature (209 patients, 216 eyes) reveals an average age at diagnosis of 17.5 years (range 2-84 years) with slight male predominance (60%). Sixty-six percent of patients are Latino, 27% are Caucasian, 5% are Black and 2% are Asian. In 53% of cases, the right eye is involved. Bilateral disease has been reported in 7 patients (4%).[2,24,27,28]
CLINICAL FEATURES
DUSN typically affects children or young adults (see Table 167.2). Usually, there are no associated systemic symptoms although cutaneous and neural larva migrans have been described in a few patients.[8,29] The vision loss, while profound, is often found incidentally due to the insidious nature of the disease. In Gass and associates' original series, half of patients are unaware of vision loss until the late stages of the disease.[2] Of symptomatic patients, the presenting complaint is often vision loss, central or paracentral scotoma.[2] Ocular discomfort is a less common complaint. The occurrence of symptoms have been reported to range from 1 day to 4 years prior to presentation.[3,26] The clinical features of DUSN manifest as early and late stages.
TABLE 167.2 -- Clinical Features of Diffuse Unilateral Subacute Neuroretinitis
|
Early Stage |
|
Vision loss |
|
Afferent pupillary defect |
|
Anterior chamber cells |
|
Hypopyon (rare) |
|
Vitritis |
|
Optic disk swelling |
|
Optic atrophy (rare) |
|
Retinal arterial narrowing |
|
Intraretinal perivascular exudation |
|
Multifocal evanescent gray-white outer retinal lesions |
|
Localized serous retinal detachment (rare) |
|
Focal intraretinal hemorrhage (rare) |
|
Choroidal neovascularization (rare) |
|
Subretinal or intraretinal tracks |
|
Motile worm: preretinal (rare), intraretinal, or subretinal |
|
Late Stage |
|
Severe vision loss |
|
Central scotoma |
|
Peripheral visual field abnormalities |
|
Relative afferent pupillary defect |
|
Optic atrophy |
|
Retinal vascular attenuation with or without sheathing |
|
Retinal pigment epithelial derangement |
|
Subretinal macular or peripapillary mass from choroidal neovascularization (rare) |
EARLY STAGE
Visual acuity in the early stage of DUSN ranges from 20/20 to hand motions, the majority being 20/200 or worse. The vision loss is often out of proportion to the visible changes of the optic nerve or retina. An afferent pupillary defect was present in 36 of 37 patients in Gass' original series, regardless of stage.[2]
In the early stage of DUSN, the external and slit-lamp eye examination is often normal. Ciliary flush, keratic precipitates, anterior chamber cell and flare have been described. Two patients presented with hypopyon.[2,30] Vitreous inflammation from mild to severe is always present. Half of patients have mild optic disk swelling. Optic atrophy has also been described in the early stage of DUSN.
Early fundus features include retinal arteriole narrowing, intraretinal perivascular exudation, pigment epithelial depigmentation and recurrent, multifocal evanescent gray-white lesions in the outer retina (Fig. 167.1). Lesions vary in size from 100 to 1200 ?m. The retinitis is typically found in one sector of the fundus and has been attributed to an inflammatory reaction against byproducts of the worm. These lesions can provide a clue as to the worm's location. The retinitis resolves in 7-10 days with minimal or no residual retinal changes. The presence and amount of retinal whitening is dependent on the activity of the organism. Localized serous retinal detachment, choroidal neovascularization, cystoid macular edema and focal intraretinal hemorrhages have been described but are less common.[2] Progressive arteriolar narrowing, optic atrophy, vitreous degeneration and pigment epithelial changes (that can simulate multifocal choroiditis or an inherited retinal degeneration) follow in the subacute phase.
|
|
|
|
FIGURE 167.1 Outer retinal whitening, retinal vasculitis and arteriolar narrowing in a patient with early stage DUSN. |
A motile intraretinal, subretinal and, in rare cases, intravitreal worm has been described in 52% of all cases in the literature (Fig. 167.2). These are commonly of two different lengths depending on the region of the world the disease is contracted. In the Southeastern United States, Caribbean, Africa, and South America, the worm is usually 400-1000 ?m in length whereas longer (1500-2000 ?m) organisms are found in the upper Midwest United States, Canada, China, and Europe. The diameter of the worm typically measures one-twentieth of its length but an organism measuring 550 ?m by 150 ?m has been described.[12] It is usually nonsegmented, white, glistening and tapered at both ends. Exposure to the examination light can cause movement in which the worm is propelled by coiling and uncoiling or wriggling in a snake-like manner. The worm often disappears and reappears over time. More than one worm has been identified in the same eye.[24] Living organisms have been identified in the eye several years after onset of symptoms and a thorough search for a worm should be carried out on all patients. Occasionally, the worm is only identified with fundus photography.
|
|
|
|
FIGURE 167.2 The 42-year-old Caucasian man from the upper Midwest United States with a 1 month history of blurred left vision (20/100) presented with (a) mild vitritis, deep retinal gray-white lesions and a motile, subretinal worm measuring 1000 ?m in length located inferotemporal to the fovea (black arrow). (b) Fluorescein angiography revealed multiple hyperfluorescent spots corresponding to areas the worm was seen migrating. (c) The patient was treated with argon laser photocoagulation (white arrow). Vision returned to 20/30 and remained stable. |
LATE STAGE
In the late or inactive stage of DUSN, vision is typically 20/200 or worse with a dense central scotoma. Visual field deficits can include the periphery. Optic atrophy and vascular attenuation (with or without sheathing) are prominent features (Fig. 167.3). There can be little correlation between the optic nerve changes and vision such that some patients with severe atrophic changes can maintain good vision and vice versa. The severity of arterial and optic nerve changes are usually consistent with one another. Vascular changes and pigment epithelial alteration can vary between different quadrants of an eye. While pigment epithelial disruption is a common feature of DUSN, pigment migration into the retina (bone spicules) is less common and not widespread when present. Greater pigment epithelial alteration has been attributed to the larger worm. A subretinal mass associated with choroidal neovascularization has been described in the macula and around the optic nerve.[2]
|
|
|
|
FIGURE 167.3 Optic atrophy and vascular narrowing in a patient with 3/200 visual acuity due to late stage DUSN. |
DIAGNOSTIC FEATURES
ANGIOGRAPHY
Fluorescein angiography in the early stage of DUSN reveals normal retinal and choroidal blood flow (see Table 167.3). Optic disk leakage is often present in eyes with nerve swelling on clinical examination. Peripheral retinal vascular changes are rarely seen in patients with active retinitis. Cystoid macular edema has been described. The focal grey-white retinal lesions are hypofluorescent in the early phase of the angiogram and stain later in the course of the study. Pigment epithelial alterations are visible as window defects but may be subtle and detected only when comparing the diseased to normal eye (Fig. 167.4).
TABLE 167.3 -- Angiographic Features of Diffuse Unilateral Subacute Neuroretinitis
|
Normal retinal and choroidal vascular filling times in the early stage |
|
Delayed retinal circulation time in the late stage |
|
Optic disk leakage |
|
Early blockage and late staining of focal retinitis when present |
|
Window defect from pigment epithelial alterations |
|
Cystoid macular edema (rare) |
|
|
|
|
FIGURE 167.4 Color fundus photograph (a) and fluorescein angiogram (b) of retinal pigment epithelial changes due to subretinal movement of a worm in a case of DUSN. |
In the late stage of DUSN, retinal circulation times may be delayed. The hyperfluorescence from pigment epithelial atrophy is most prominent around the optic nerve and in the midperipheral retina. The macula usually only demonstrates mottled hyperfluorescence except in cases of disciform scar formation.
Serial indocyanine green (ICG) angiographic findings have been described in one patient with DUSN in which a worm was identified.[31] Findings in both the early and late stage of the disease include hypofluorescence of the clinically visible lesions in the early and intermediate phases of the study with persistent changes of only a few of the lesions in the late frames of the study. There was also ill-defined hyperfluorescence in the macular area in both phases of the disease. The authors suggest that choroidal infiltration was the cause of the angiographic pattern.
ELECTROPHYSIOLOGY
Electroretinographic (ERG) abnormalities of only the affected eye were present in all but one patient in Gass and Scelfo's original series.[1] The unaffected eye is normal in all electrophysiologic parameters. In the affected eye, both rod and cone function is typically abnormal, with a reduction of the b:a-wave ratio, suggestive of proportionately inner retinal injury. Electrooculography was noted as subnormal in 16 of 29 in the original series.
Electrophysiologic deterioration is progressive as suggested by a case report of a 9-year-old Caucasian boy with serial electrophysiologic testing over 4 years.[32] In this patient (who had poor vision at presentation), pattern visual-evoked potential and pattern ERG, indicators of visual pathways and macular photoreceptor function, respectively, both progressed from nearly extinguished to undetectable over a year. Full-field ERG demonstrated progressive inner retinal dysfunction as suggested by reduced b-wave amplitudes and additional photoreceptor involvement, but, in keeping with Gass and associates' findings, never became completely extinguished.[32]
Multifocal electroretinography (mfERG) was described in one patient in early stage DUSN with good vision.[9] The decreased foveal response density as well as the increased parafoveal and perifoveal waveform amplitudes fully recovered after successful laser ablation of the parasite.
OTHER STUDIES
There has been no consistently positive serum, urine or stool assays in patients with DUSN. In an analysis by Gass and coworkers, serum antibody titers to Toxocara canis by enzyme-linked immunosorbent assay (ELISA) was present in five of 14 eyes in which the smaller worm was identified.[7] None of these titers met the Centers for Disease Control defiition of a positive test. Eosinophilia is rare in DUSN.
Scanning laser ophthalmoscopy (SLO) has been used to study four eyes of three patients with DUSN.[28] The authors used the argon blue (488nm wavelength) laser to provide high contrast for identification of the worm and helium-neon (633nm) laser energy to perform perimetry and identify scotoma associated with damage associated with the worm. They suggest that SLO may be more sensitive and better tolerated than clinical examination or fundus photography in detecting the often elusive parasite.[28]
DIFFERENTIAL DIAGNOSIS
The differential diagnosis for DUSN is broad and varies depending on the stage at presentation. In the early stage of the disease, optic nerve swelling and vitritis may mimic intermediate uveitis or optic neuritis. The outer retinal lesions can be mistaken for multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, multifocal choroiditis and panuveitis, serpiginous choroiditis, multifocal outer retinal toxoplasmosis, sarcoidosis, syphilis, Behçet's disease or large-cell lymphoma.
In the late stages of the disease when pigment epithelial derangement, vascular narrowing and optic atrophy are the predominant features of the disease, the differential diagnosis includes multifocal choroiditis with panuveitis, central or ophthalmic artery obstruction, optic neuropathy from a compressive orbital lesion, Behçet's disease, large cell lymphoma, inactive acute retinal necrosis, atypical retinitis pigmentosa, retained ferrous-containing metallic foreign body or posttraumatic chorioretinopathy. Careful history and serial ophthalmic examinations will help to differentiate the conditions listed above from DUSN.
PATHOPHYSIOLOGY
It is accepted that DUSN is a form of ocular larval migrans and that vision loss is associated with the parasite movement through and under the retina. The clinical and electrophysiology data suggest damage to both the retina and optic nerve.[32] Proposed mechanisms of vision loss include: (1) direct toxic effects of the worm's excretory-secretory proteins or (2) a result of the host inflammatory reaction to the parasite (3) mechanical damage caused by movement of the worm or (4) an autoimmune reaction somehow initiated by the infection.[2,7,32]
The toxic effect of the worm has been described as both local and diffuse. The local effects are manifest in the focal, evanescent retinal lesions that seem to coincide with the worm's migration while the diffuse effects are manifest in the rapid vision loss and global retinal and optic nerve dysfunction.[7] While no specific causative toxin has been identified in DUSN, eosinophil-derived neurotoxin and major basic protein have been implicated in neural larval migrans with Baylisascaris procyonis.[33]
The exact identity of the parasite in most cases is not known. Multicellular parasites exist in two distinct phyla: nemahelminthes (roundworms or nematodes) and platyhelminthes (flatworms, containing classes trematoda and cestoda). A large number of helminthes have the potential to cause ocular larval migrans. Species implicated in DUSN include several nematodes: Toxocara canis, Baylisascaris procyonis, Ancylostoma caninum, Ascaris lumbricoides and Dirofilaria spp.[8,29,34-38] One trematode, Alaria mesocercaria, has been identified as causing DUSN.[12]
At least two distinct worms are responsible for DUSN. Investigators have speculated that the smaller (400-1000 ?m) worm found in Southeast US, the Caribbeans, and South America is Toxocara canis or Ancylostoma caninum. While serologic evidence supports the diagonis of T. canis in some cases, the majority do not have positive serology, eosinophilia or granuloma characteristic of toxocariasis.[6,7,37]
Baylisascaris procyonis has been implicated in DUSN due to the larger (1500-2000 ?m) nematode found in the upper Midwest US, Canada, China and Europe. Investigators have found retinal lesions consistent with DUSN in animal models experimentally infected with B. procyonis eggs.[39,40] Goldberg and coworkers describe a case of DUSN in which the patient had serologic evidence of Baylisascaris exposure and necropsy of several raccoons around the patient's home revealed adult B. procyonis in the intestines and infective eggs in the feces of 8/12 (67%) animals tested. Concurrent ocular and neural larval migrans have been described in two children with a history of pica living in an area endemic for raccoons. Both had high cerebrospinal fluid and serum titers to B. procyonis.
The parasite has been successfully removed via eye wall resection[41] and vitrectomy[12,35,38] in a total of four patients. Identification of surgically removed specimens has proven challenging. Gass described features of Ancylostoma caninum but exact identification could not be made. de Souza and coworkers described the findings of a 630 × 30 ?m worm with morphologic features most consistent with T. canis but because of poor fixation, the definite identification remains uncertain.[35] Others who have reviewed photomicrographs of this case have suggested the organism is Ancylostoma.[29] A larger worm measuring 4500 ?m was lost in transport to the parasitology lab.[38] McDonald and coworkers removed and identified a pathogen as Alaria mesocercaria.[12] This is clearly not the cause of the majority of DUSN cases as the shape (550 × 190 ?m) and movement differs greatly.
TREATMENT
Laser photocoagulation of the motile worm has been shown to halt disease progression in DUSN.[5,7,10,12,17,20,23,42-44] In 1978, Raymond and coworkers were the first to report the use of xenon (one patient) and argon (one patient) laser photocoagulation to destroy a motile worm. Vision improvement and resolution of inflammation was noted in both patients.[5]
Improved visual acuity with laser photocoagulation has since been confirmed in early stage DUSN. Garcia reported four cases treated with laser relatively early in the course of the disease. The two patients treated within a month of symptom onset had the best outcomes.[43] In a large series of patients with late stage DUSN, vision stabilization was achieved in 19 of 22 patients, with improvement in only one.[26]There have been no reported complications of laser for DUSN. While confluent treatment of the larvae has most often been employed, treatment of the advancing end of the worm has been successful in a case when treatment of the entire worm would jeopardize the fovea (Fig. 167.5).[21]
|
|
|
|
FIGURE 167.5 The 29-year-old Caucasian man from Northern California with a 3 week history of right transient visual obscurations. Initial vision was 20/20 in the right eye with optic nerve swelling and a trace afferent pupillary defect. Serial examination over 6 weeks led to the discovery of a (a) motile subretinal worm within the macula (magnified in inset). (b) Examination after initial thermal laser phototcoagulation (white arrow) revealed the worm had moved superotemporal to the fovea. A second session of laser (black arrow) was performed. The motile tail end of the worm was not treated due to proximity to the fovea. (c) After destruction of the worm, the vision stabilized at 20/25. |
Medical therapy for DUSN has produced mixed results. Rubin was the first to report using a combination of oral prednisone (40 mg/day for 3 weeks) and thiabendazole (2 g/day for 5 days) in a 31 year-old woman with early stage DUSN and progressive vision loss.[6] Three months after treatment the vision improved from 20/200 to 20/60 and there was reduction of scotoma size and intraocular inflammation. Subsequently, Gass and Braunstein reported patients treated with thiabendazole (with or without steroids) or diethylcarbamazine citrate in which the worm remained viable. They postulated that the drug could not cross the blood-retinal barrier at larvacidal concentrations. A later study by Gass and coworkers suggest that thiabendazole could be effective in some patients, especially those with moderate or severe vitritis.[45] One patient treated with ivermectin had continued nematode movement and subsequently required laser photocoagulation.[42]
Recently, success has been achieved with a 1 month course of high dose (400 mg/day) albendazole (without corticosteroids) in patients with the small worm variant of DUSN.[25] The authors report improved inflammation, stable or improved vision and resolution of worm motility. Cortez and colleagues treated six patients in which a motile worm was identified with a 10-day course of albendazole (600 mg/day). The worm remained viable in half (three) of the patients, necessitating laser.
CONCLUSION
DUSN represents a form of ocular larva migrans that is likely caused by many different helminthes and leads to global retinal and optic nerve dysfunction. Early recognition of the disease is essential to maintaining, and in some cases, improving vision. A detailed search for the motile larvae (including serial biomicroscopy and color fundus photography) should be carried out in all stages of the DUSN as destruction of the worm can halt disease progression. While most patients are otherwise healthy, cutaneous, visceral or neural larva migrans may occur.
Laser photocoagulation should be considered as first-line therapy in patients in whom the motile larvae are identified, provided treatment will spare the central macula. For the 50% of patients in whom a worm cannot be found, a month-long course of albendazole should be considered.
REFERENCES
1. Gass JD, Scelfo R: Diffuse unilateral subacute neuroretinitis. J R Soc Med 1978; 71:95-111.
2. Gass JD, Gilbert Jr WR, Guerry RK, Scelfo R: Diffuse unilateral subacute neuroretinitis. Ophthalmology 1978; 85:521-545.
3. PARSONS HE: Nematode chorioretinitis; report of a case, with photographs of a viable worm. AMA Arch Ophthalmol 1952; 47:799-800.
4. Price Jr JA, Wadsworth JA: An intraretinal worm. Report of a case of macular retinopathy caused by invasion of the retina by a worm. Arch Ophthalmol 1970; 83:768-770.
5. Raymond LA, Gutierrez Y, Strong LE, et al: Living retinal nematode (filarial-like) destroyed with photocoagulation. Ophthalmology 1978; 85:944-949.
6. Rubin ML, Kaufman HE, Tierney JP, Lucas HC: An intraretinal nematode (a case report). Trans Am Acad Ophthalmol Otolaryngol 1968; 72:855-866.
7. Gass JD, Braunstein RA: Further observations concerning the diffuse unilateral subacute neuroretinitis syndrome. Arch Ophthalmol 1983; 101:1689-1697.
8. 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 Bbaylisascaris procyonis. Am J Ophthalmol 2003; 135:888-890.
9. Martidis A, Greenberg PB, Rogers AH, et al: Multifocal electroretinography response after laser photocoagulation of a subretinal nematode. Am J Ophthalmol 2002; 133:417-419.
10. Sivalingam A, Goldberg RE, Augsburger J, Frank P: Diffuse unilateral subacute neuroretinitis. Arch Ophthalmol 1991; 109:1028.
11. Goldberg MA, Kazacos KR, Boyce WM, et al: Diffuse unilateral subacute neuroretinitis. Morphometric, serologic, and epidemiologic support for Baylisascaris as a causative agent. Ophthalmology 1993; 100:1695-1701.
12. McDonald HR, Kazacos KR, Schatz H, Johnson RN: Two cases of intraocular infection with Alaria mesocercaria (Trematoda). Am J Ophthalmol 1994; 117:447-455.
13. Yuen VH, Chang TS, Hooper PL: Diffuse unilateral subacute neuroretinitis syndrome in Canada. Arch Ophthalmol 1996; 114:1279-1282.
14. Salvanet-Bouccara A, Troussier H: Diffuse unilateral subacute neuroretinitis. Apropos of a case. J Fr Ophtalmol 1987; 10:667-672.
15. Kinnear FB, Hay J, Dutton GN, Smith HV: Presumed ocular larva migrans presenting with features of diffuse unilateral subacute neuroretinitis. Br J Ophthalmol 1995; 79:1140-1141.
16. Bernasconi OR, Piguet B: Unilateral diffuse subacute neuroretinitis. Klin Monatsbl Augenheilkd 1997; 210:327-328.
17. Kuchle M, Knorr HL, Medenblik-Frysch S, et al: 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.
18. Meyer-Riemann W, Petersen J, Vogel M: An attempt to extract an intraretinal nematode located in the papillomacular bundle. Klin Monatsbl Augenheilkd 1999; 214:116-119.
19. Rasquin F, Waterschoot MP, Termote H, Carlier Y: Diffuse unilateral subacute neuroretinitis in Africa. Ocul Immunol Inflamm 2006; 14:59-62.
20. Carney MD, Combs JL: Diffuse unilateral subacute neuroretinitis. Br J Ophthalmol 1991; 75:633-635.
21. Myint K, Sahay R, Mon S, et al: 'Worm in the Eye' - The Rationale for treatment of DUSN in South India. Br J Ophthalmol 2006; 90:1125-1127.
22. Cai J, Wei R, Zhu L, et al: Diffuse unilateral subacute neuroretinitis in China. Arch Ophthalmol 2000; 118:721-722.
23. de Souza EC, da Cunha SL, Gass JD: Diffuse unilateral subacute neuroretinitis in South America. Arch Ophthalmol 1992; 110:1261-1263.
24. Cortez R, Denny JP, Muci-Mendoza R, et al: Diffuse unilateral subacute neuroretinitis in Venezuela. Ophthalmology 2005; 112:2110-2114.
25. 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.
26. de Garcia CA, Gomes AH, Vianna RN, et al: Late-stage Diffuse Unilateral Subacute Neuroretinitis: Photocoagulation of the Worm does not Improve the Visual Acuity of Affected Patients. Int Ophthalmol 2006; 26:39-42.
27. 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.
28. 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.
29. Gass JDM: Stereoscopic atlas of macular diseases, 4th edn.. St Louis: Mosby; 1997:622-628.
30. Muccioli C, Belfort Jr R: Hypopyon in a patient with presumptive diffuse unilateral subacute neuroretinitis. Ocul Immunol Inflamm 2000; 8:119-121.
31. Vianna RN, Onofre G, Ecard V, et al: Indocyanine green angiography in diffuse unilateral subacute neuroretinitis. Eye 2006; 20:1113-1116.
32. Audo I, Webster AR, Bird AC, et al: Progressive retinal dysfunction in diffuse unilateral subacute neuroretinitis. Br J Ophthalmol 2006; 90:793-794.
33. Moertel CL, Kazacos KR, Butterfield JH, et al: Eosinophil-associated inflammation and elaboration of eosinophil-derived proteins in 2 children with raccoon roundworm (Baylisascaris procyonis) encephalitis. Pediatrics 2001; 108:E93.
34. Ashton N: Larval granulomatosis of the retina due to Toxocara. Br J Ophthalmol 1960; 44:129-148.
35. de Souza EC, Nakashima Y: Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology 1995; 102:1183-1186.
36. Kazacos KR, Vestre WA, Kazacos EA, Raymond LA: Diffuse unilateral subacute neuroretinitis syndrome: probable cause. Arch Ophthalmol 1984; 102:967-968.
37. Oppenheim S, Rogell G, Peyser R: Diffuse unilateral subacute neuroretinitis. Ann Ophthalmol 1985; 17:336-338.
38. Yamamoto S, Hayashi M, takeuchi S: Surgically removed submacular nematode. Br J Ophthalmol 1999; 83:1088.
39. Akao N, Hayashi E, Sato H, et al: Diffuse retinochoroiditis due to Baylisascaris procyonis in Monglian gerbils. J Parasitol 2003; 89:174-175.
40. Kazacos KR, Raymond LA, Kazacos EA, Vestre WA: The raccoon ascarid. A probable cause of human ocular larva migrans. Ophthalmology 1985; 92:1735-1744.
41. Gass JDM: Stereoscopic atlas of macular diseases, 3rd edn.. St Louis: CV Mosby; 1987:474-475.
42. Casella AM, Farah ME, Belfort Jr R: Antihelminthic drugs in diffuse unilateral subacute neuroretinitis. Am J Ophthalmol 1998; 125:109-111.
43. Garcia CA, Gomes AH, Garcia Filho CA, Vianna RN: Early-stage diffuse unilateral subacute neuroretinitis: improvement of vision after photocoagulation of the worm. Eye 2004; 18:624-627.
44. Matsumoto BT, Adelberg DA, Del Priore LV: Transretinal membrane formation in diffuse unilateral subacute neuroretinitis. Retina 1995; 15:146-149.
45. Gass JD, Callanan DG, Bowman CB: Oral therapy in diffuse unilateral subacute neuroretinitis. Arch Ophthalmol 1992; 110:675-680.
46. Myint K, Sahay R, Mon S, et al: The Indian case of live worm in Diffuse Unilateral Subacute Neuroretinitis. Eye 2006; 20:612-613.
47. Cialdini AP, de Souza EC, Avila MP: The first South American case of diffuse unilateral subacute neuroretinitis caused by a large nematode. Arch Ophthalmol 1999; 117:1431-1432.
48. Harto MA, Rodriguez-Salvador V, Avino JA, et al: Diffuse unilateral subacute neuroretinitis in Europe. Eur J Ophthalmol 1999; 9:58-62.
49. Gass JD: Subretinal migration of a nematode in a patient with diffuse unilateral subacute neuroretinitis. Arch Ophthalmol 1996; 114:1526-1527.
