eMedicine Specialties > Ophthalmology > Retina
Neuroretinitis, Diffuse Unilateral Subacute
Updated: May 26, 2009
Introduction
Background
Diffuse unilateral subacute neuroretinitis (DUSN) is a progressive parasitic disease affecting the outer retina and retinal pigment epithelium (RPE). This syndrome is primarily unilateral, although bilateral cases have occurred. The ocular findings include visual loss, vitreous cells, optic disc inflammation and leakage, and transient recurrent crops of gray-white outer retinal lesions.
Stationary or migrating nematodes have been identified deep in the retina or in the subretinal space. Later in the course of the disease, slowly progressive RPE changes and optic atrophy may be observed, as well as narrowing of the retinal vessels.
Pathophysiology
The exact pathophysiology is uncertain, but the local inflammatory changes may be related to toxic effects or immunologic stimulation from excretory products of the larva or from release of unknown soluble tissue toxins. The fleeting gray-white lesions in the outer retina appear to be a local reaction to noxious stimulation. The loss of vision and progressive optic atrophy secondary to death of ganglion cells and neural fibers may be a remote reaction to soluble toxins.
Frequency
United States
The southeast and the upper Midwest are known endemic areas for the disease.
International
DUSN has been reported initially in the Caribbean islands, Brazil, Ghana, and Germany. In the last few years, DUSN has been reported in many other countries, including China, India, South Africa, and Spain.
Mortality/Morbidity
- No cases of mortality have been reported. Four cases of severe neurologic degeneration with DUSN have been reported in children.
- The natural history of untreated DUSN involves multiple recurrent episodes of diffuse and focal inflammation of the retina and RPE with secondary progressive visual loss and optic atrophy in the affected eye.
- It rarely affects the fellow eye. Only 2 cases with bilateral involvement have been reported.
Race
DUSN does not show any particular racial preference.
Sex
This condition occurs more frequently in males than in females.
Age
It occurs most frequently in the second and third decades. Young children and older adults also may be affected.
Clinical
History
- Early stage
- Mild-to-moderate visual loss
- Paracentral or central scotomas
- Floaters
- Ocular discomfort
- Conjunctival injection of affected eye
- Late stage
- Severe unilateral visual loss
- Paracentral or central scotomas
- In some patients, the disease may be asymptomatic with the characteristic changes found only on routine eye examination.
Physical
Patients should undergo a complete eye examination, including visual acuity, pupillary reactions, visual fields, slit lamp examination of the anterior and posterior segments, indirect ophthalmoscopy, and detailed examination of the retina using a fundus contact lens.
- Early stage
- Visual acuity - Range is from 20/30 to 20/200 or less.
- Visual field - Paracentral or central scotoma may be detected.
- Pupils - A relative afferent pupillary defect may be noted.
- Anterior segment findings reveal normal conjunctiva or conjunctival injection, ciliary flush, anterior chamber cells and flare, fine keratic precipitates, and small hypopyon.
- Posterior segment examination findings reveal mild-to-moderate vitritis, optic disc swelling, narrowing of the retinal arterioles, retinitis, and nematodes.
- Retinitis is the most characteristic feature of this syndrome. Transient, multiple, focal, gray-white lesions of the deep retina or RPE vary in size from 0.25-1 disc diameter and tend to develop in clusters over wide areas of the retina at various time periods. The active evanescent gray-white lesions fade within a period of 7-10 days as the nematode moves elsewhere in the eye, only to recur in an adjacent area or distant site over the ensuing weeks. Lesions typically resolve without any ophthalmoscopic or angiographic evidence of damage.
- Nematode: Identification of the subretinal worm is the pathognomonic finding in DUSN. To localize the worm, careful and repeated examination with a fundus contact lens is required. The worm can be present in all layers of the retina, but it most frequently is found in the subretinal or outer retinal layers. The motile worm is more likely to be observed in the neighborhood of the active grayish-white retinal lesions. The worms appear smooth in outline, tapered on both ends, and often assume an S-shaped, coiled, or figure "8" configuration. These organisms propel themselves by a coiling and uncoiling motion and sometimes move in a snakelike fashion in the subretinal space. They may be noted to move under direct observation in an apparent aversion to bright light, and a white glistening sheen may be noted over the region.
- Other less frequently encountered clinical signs include the following: focal retinal and subretinal hemorrhages, perivenous exudates and vascular sheathing, localized serous detachments of the neurosensory retina, cystoid macular edema, retinal striae, and choroidal neovascularization.
- Late stage
- Visual acuity - Typically less than 20/400
- Visual fields - Dense central or paracentral scotoma may be seen.
- Pupils - Relative afferent pupillary defect possible
- Posterior segment examination reveals the following findings:
- Focal and diffuse loss or mottling of the RPE, most typically seen in the paramacular region, sparing the center of the macula in most patients
- Generalized narrowing of the retinal arterioles
- Marked optic disc pallor
- Choroidal neovascularization and/or disciform scarring
- Peripapillary arteriolar sheathing
Causes
- Precise identification of the worm has not been accomplished, but two different types of worms have been recognized in endemic areas.
- In the southeastern United States, Caribbean, and Latin America, a larval worm measuring about 400-700 µm has been recognized. It is presumed to be Ancylostoma canium, which is a known frequent cause of cutaneous larval migrans.
- In the north midwestern United States, a larger worm measuring 1000-2000 µm has been observed. It is proposed by some authors to be Baylisascaris procyonis and is a rare cause of visceral and ocular larval migrans.
Differential Diagnoses
Papilledema
Presumed Ocular Histoplasmosis Syndrome
Sarcoidosis
Toxoplasmosis
White Dot Syndromes
Other Problems to Be Considered
Early stage
Active retinal lesions include the following:
Toxoplasmosis
Cytomegalovirus retinitis
Fungal or bacterial retinal abscesses
Acute posterior multifocal placoid pigment epitheliopathy
Multiple evanescent white dot syndrome
Serpiginous choroiditis
Behçet disease
Pseudo–presumed ocular histoplasmosis syndrome
Multifocal choroiditis
Perivasculitis includes sarcoidosis
Optic disc swelling includes acute neuroretinitis and papilledema
Vitritis includes pars planitis
Late stage
Retinal pigment epithelial atrophy includes the following:
Presumed ocular histoplasmosis syndrome
Unilateral retinitis pigmentosa
Traumatic chorioretinopathy
Chorioretinal atrophy after ophthalmic artery occlusion
Optic atrophy includes the following:
Secondary to optic neuritis
Compressive lesions
Ischemic optic neuropathy
Workup
Laboratory Studies
- Serologic studies for parasites, analysis of stool for ova and parasites, and hematologic evaluation for eosinophilia are of limited value in establishing the diagnosis of DUSN.
- Some serological tests may be indicated to exclude other diseases.
Imaging Studies
- Fluorescein angiography is useful for monitoring the status of the inflammation.
- Early stage of the disease
- Leakage from the optic nerve head capillaries and some generalized paravenous leakage
- Window defects indicating minimal changes in the RPE
- Staining of the clinically apparent gray-white lesions during the later phases of the angiogram, which are nonfluorescent in the early phase
- Cystoid macular edema in some patients
- Late stages of the syndrome
- Diffuse areas of focal hyperfluorescence secondary to RPE loss
- Leakage from choroidal neovascularization
- Early stage of the disease
- Scanning laser ophthalmoscope
- Although an examination with a fundus contact lens by a skilled ophthalmologist is the method of choice, the scanning laser ophthalmoscope (SLO) provides a new examination modality with distinct advantages for identifying live worms in young patients with DUSN. The infrared laser is safe and comfortable for a prolonged examination.
- Using blue illumination, the ocular fundus appears dark and provides a high-contrast background for the white image of the worm. The red perimetry laser stimulus can be used to stimulate the worm's movement and to pinpoint its location.
Other Tests
- An electroretinogram (ERG) is used to objectively evaluate the functional status of the retina and to differentiate from other retinal conditions.
- In the affected eye, the ERG usually is reduced in all stages of the disease.
- It is often moderately or severely reduced in the later stages of the disease.
- The b-wave is affected more than the a-wave.
- Rarely, the ERG may be extinguished completely.
- ERG findings are normal in the unaffected eye.
- ERG performed before and after laser photocoagulation appears to be useful in monitoring the retinal findings. After laser photocoagulation, recovery of ERG findings may be documented.
- Electro-oculogram (EOG) findings are abnormal in approximately 50% of patients.
- Visual field
- Paracentral and central visual field defects
- Useful to monitor the visual field over a period of time and to differentiate from other conditions
Histologic Findings
The only histologic findings are from an enucleated eye presumed to have DUSN. Histopathology showed nongranulomatous vitritis, retinitis, and retinal and optic nerve perivasculitis. RPE and low-grade, patchy nongranulomatous choroiditis were observed. There was no evidence of a worm.
Treatment
Medical Care
- Laser photocoagulation of the nematode is the treatment of choice. Direct laser photocoagulation has been effective in destroying the worm. In early stages of DUSN, prompt localization and destruction of the worm by photocoagulation may improve the vision of patients, and, in other situations, the progression of the disease is halted. No significant intraocular inflammation has been associated with this treatment.
- Antihelminthic treatment is being used more frequently. It may be considered when the organism cannot be found.
Surgical Care
- Although direct laser photocoagulation of the nematode is the treatment of choice for DUSN, surgical transvitreal removal of the nematode may be indicated in selected cases.
- Pars plana vitrectomy and removal of an intact parasite by various vitrectomy instrumentation allow removal of the nematode for parasitologic identification.
- In addition, the inflammation may completely subside with recovery of function.
Consultations
Consultation with a uveitis or retinal specialist is often useful for patients with suspected DUSN.
Medication
Antihelminthic treatment is for patients with moderate-to-severe vitreous inflammation or when it is not possible to locate and treat the nematode with photocoagulation. However, it is not effective in destroying the organism in all patients, especially in those with minimal vitreous inflammation where the drug has low ocular penetration.
Thiabendazole is the drug of choice for initial medical therapy. Successful treatment is characterized by the development of a localized area of intense retinitis and fading of the grayish-white retinal lesions within 10 days after completion of therapy.
Ivermectin may be considered if thiabendazole is not effective or cannot be tolerated.
High-dose oral albendazole seems to be safe and beneficial for patients with active DUSN in the early or late clinical stage.
Anthelmintics
Vermicidal drugs that kill the organism by various antihelminthic actions.
Thiabendazole (Mintezol)
An antihelminthic agent. Probably acts by inhibiting the helminth-specific enzyme fumarate reductase. Vermicidal and/or vermifugal.
Dosing
Adult
22 mg/kg PO bid for 2-4 successive d in patients with moderate-to-severe vitritis; not to exceed 3 g/d
More recently, 25 mg/kg/d PO qhs for 25 d has been recommended
Pediatric
Administer as in adults; in pediatric patients <30 lb, safety and effectiveness is limited
Interactions
When used concomitantly with xanthine derivatives, it may be necessary to monitor the blood levels and/or reduce the dosage of such compounds
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Frequent adverse effects include nausea, vomiting, anorexia, and mild central nervous system disturbances such as dizziness, drowsiness, or headache
Ivermectin (Stromectol)
A semisynthetic, anthelmintic agent mainly used for filarial worms. Effectiveness in the treatment of DUSN is unclear.
Dosing
Adult
150 µg/kg PO once
Pediatric
Administer as in adults; not established in pediatric patients <15 kg
Interactions
Excreted by the liver
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Frequent adverse effects include nausea, vomiting, anorexia, and mild central nervous system disturbances
Albendazole (Albenza)
A benzimidazole carbamate drug that inhibits tubulin polymerization, resulting in degeneration of cytoplasmic microtubules. Decreases ATP production in the worm, causing energy depletion, immobilization, and finally death. Converted in the liver to its primary metabolite, albendazole sulfoxide. Less than 1% of the primary metabolite is excreted in the urine. Plasma level is noted to rise significantly (as much as 5-fold) when ingested after high-fat meal. Experience with patients <6 y is limited. To avoid inflammatory response in CNS, patient must also be started on anticonvulsants and high-dose glucocorticoids.
Dosing
Adult
400 mg PO qd for 30 d has been used
Pediatric
<15 kg: Not established
>15 kg: Administer as in adults
Interactions
Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue use if LFTs increase significantly (resume when levels decrease to pretest values); abdominal pain, nausea, vomiting, diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and alopecia may occur
Follow-up
Further Outpatient Care
- The patients should be observed closely until the organism is identified for focal laser photocoagulation.
- Patients should receive follow-up evaluations every 1-2 weeks until the inflammation resolves.
Prognosis
- DUSN is a condition in which prompt identification and destruction of the infecting nematode can result in the cessation of symptoms and the preservation of good visual acuity. If untreated, the disease progressively damages the retina and the optic nerve, leading to severe visual loss.
Patient Education
- If the vision is reduced substantially in one eye, then emphasis should be made regarding monocular precautions and the use of protective safety glasses.
Miscellaneous
Medicolegal Pitfalls
- In view of the extensive differential diagnoses and uncommon conditions that mimic DUSN, it is important to consult with a uveitis or retina specialist.
References
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Cialdini AP, de Souza EC, Avila MP. The first South American case of diffuse unilateral subacute neuroretinitis caused by a large nematode. Arch Ophthalmol. Oct 1999;117(10):1431-2. [Medline].
de Souza EC, Abujamra S, Nakashima Y, Gass JD. Diffuse bilateral subacute neuroretinitis: first patient with documented nematodes in both eyes. Arch Ophthalmol. Oct 1999;117(10):1349-51. [Medline].
de Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology. Aug 1995;102(8):1183-6. [Medline].
Garcia CA, Gomes AH, Garcia Filho CA, Vianna RN. Early-stage diffuse unilateral subacute neuroretinitis: improvement of vision after photocoagulation of the worm. Eye. Jun 2004;18(6):624-7. [Medline].
Gass JD, Callanan DG, Bowman CB. Oral therapy in diffuse unilateral subacute neuroretinitis. Arch Ophthalmol. May 1992;110(5):675-80. [Medline].
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Gass JDM. Diffuse unilateral subacute neuroretinitis. In: Stereoscopic Atlas of Macular Disease: Diagnosis and Treatment. 4th ed. 1997:622-628.
Harto MA, Rodriguez-Salvador V, Aviñó JA, Duch-Samper AM, Menezo JL. Diffuse unilateral subacute neuroretinitis in Europe. Eur J Ophthalmol. Jan-Mar 1999;9(1):58-62. [Medline].
Martidis A, Greenberg PB, Rogers AH, Velázquez-Estades LJ, Baumal CR. Multifocal electroretinography response after laser photocoagulation of a subretinal nematode. Am J Ophthalmol. Mar 2002;133(3):417-9. [Medline].
Mets MB, Noble AG, Basti S, Gavin P, Davis AT, Shulman ST, 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. Jun 2003;135(6):888-90. [Medline].
Meyer-Riemann W, Petersen J, Vogel M. [An attempt to extract an intraretinal nematode located in the papillomacular bundle]. Klin Monatsbl Augenheilkd. Feb 1999;214(2):116-9. [Medline].
Moraes LR, Cialdini AP, Avila MP, Elsner AE. Identifying live nematodes in diffuse unilateral subacute neuroretinitis by using the scanning laser ophthalmoscope. Arch Ophthalmol. Feb 2002;120(2):135-8. [Medline].
Myint K, Sahay R, Mon S, Saravanan VR, Narendran V, Dhillon B. The Indian case of live worm in diffuse unilateral subacute neuroretinitis. Eye. May 2006;20(5):612-3. [Medline].
Slakter JS, Ciardella AP. Diffuse unilateral subacute neuroretinitis. Retina Vitreous Macula. 1998;806-812.
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. Sep 2005;140(3):437-445. [Medline].
Keywords
diffuse unilateral subacute neuroretinitis, DUSN, diffuse bilateral subacute neuroretinitis, unilateral wipeout syndrome
Contributor Information and Disclosures
Author
Lakshmana M Kooragayala, MD, Vitreo-retinal Surgeon, Marietta Eye Clinic
Lakshmana M Kooragayala, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, and Medical Association of Georgia
Disclosure: Nothing to disclose.
Medical Editor
Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Managing Editor
R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.
CME Editor
Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.