dusn

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Neuroretinitis, Diffuse Unilateral

Subacute

ntroduction

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 thesubretinal 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 berelated 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 aremote 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.

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• 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

o Mild-to-moderate visual loss

o Paracentral or central scotomas

o Floaters

o Ocular discomforto Conjunctival injection of affected eye

• Late stage

o Severe unilateral visual loss

o 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 contactlens.

• Early stage

o Visual acuity - Range is from 20/30 to 20/200 or less.

o Visual field - Paracentral or central scotoma may be detected.

o Pupils - A relative afferent pupillary defect may be noted.

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o Anterior segment findings reveal normal conjunctiva or conjunctival

injection, ciliary flush, anterior chamber cells and flare, fine keratic

precipitates, and small hypopyon.o 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 inclusters 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 inan 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, carefuland repeated examination with a fundus contact lens is required.

The worm can be present in all layers of the retina, but it mostfrequently 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 smoothin 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 notedto 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, andchoroidal neovascularization.

• Late stage

o Visual acuity - Typically less than 20/400

o Visual fields - Dense central or paracentral scotoma may be seen.

o Pupils - Relative afferent pupillary defect possible

o Posterior segment examination reveals the following findings:

Focal and diffuse loss or mottling of the RPE, most typically seenin 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

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Causes

• Precise identification of the worm has not been accomplished, but two different

types of worms have been recognized in endemic areas.o 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 cutaneouslarval migrans.

o 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 SyndromeSarcoidosis

Toxoplasmosis

White Dot Syndromes

Other Problems to Be Considered

Early stage

Active retinal lesions include the following:

Toxoplasmosis Cytomegalovirus retinitisFungal or bacterial retinal abscesses

Acute posterior multifocal placoid pigment epitheliopathy

Multiple evanescent white dot syndromeSerpiginous choroiditis

Behçet disease

Pseudo–presumed ocular histoplasmosis syndromeMultifocal 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:

http://emedicine.medscape.com/article/1217204-overview












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Presumed ocular histoplasmosis syndrome

Unilateral retinitis pigmentosa

Traumatic chorioretinopathyChorioretinal atrophy after ophthalmic artery occlusion

Optic atrophy includes the following:

Secondary to optic neuritis

Compressive lesionsIschemic 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 thediagnosis 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.

o 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 thelater phases of the angiogram, which are nonfluorescent in the

early phase Cystoid macular edema in some patients

o Late stages of the syndrome

Diffuse areas of focal hyperfluorescence secondary to RPE loss Leakage from choroidal neovascularization

• Scanning laser ophthalmoscope

o 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. Theinfrared laser is safe and comfortable for a prolonged examination.

o 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.




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Other Tests

• An electroretinogram (ERG) is used to objectively evaluate the functional status

of the retina and to differentiate from other retinal conditions.o In the affected eye, the ERG usually is reduced in all stages of the disease.

o It is often moderately or severely reduced in the later stages of the disease.o The b-wave is affected more than the a-wave.

o Rarely, the ERG may be extinguished completely.

o ERG findings are normal in the unaffected eye.

o 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

o Paracentral and central visual field defects

o Useful to monitor the visual field over a period of time and to differentiatefrom 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 mayimprove 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 choicefor DUSN, surgical transvitreal removal of the nematode may be indicated in

selected cases.

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o Pars plana vitrectomy and removal of an intact parasite by various

vitrectomy instrumentation allow removal of the nematode for

parasitologic identification.o 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 thegrayish-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• Interactions

• Contraindications

• Precautions

Adult

http://www.medscape.com/resource/uveitis-ocular-immunology

http://www.medscape.com/resource/uveitis-ocular-immunology

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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

• Dosing

• Interactions


• Precautions

When used concomitantly with xanthine derivatives, it may be necessary to monitor the

blood levels and/or reduce the dosage of such compounds

•

Dosing• Interactions


• Precautions

Documented hypersensitivity

• Dosing

• Interactions


• 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 nervoussystem 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

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• Interactions


• Precautions

Adult

150 µg/kg PO once

Pediatric

Administer as in adults; not established in pediatric patients <15 kg

• Dosing

• Interactions


• Precautions

Excreted by the liver

• Dosing

• Interactions


• Precautions

Documented hypersensitivity

• Dosing•

Interactions• Contraindications

• 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 nervoussystem disturbances

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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 isexcreted 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 avoidinflammatory response in CNS, patient must also be started on anticonvulsants and high-

dose glucocorticoids.

• Dosing

• Interactions


• Precautions

Adult

400 mg PO qd for 30 d has been used

Pediatric

<15 kg: Not established

>15 kg: Administer as in adults

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 theinflammation 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 preservationof good visual acuity. If untreated, the disease progressively damages the retina

and the optic nerve, leading to severe visual loss.

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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.

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