Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

Figures 3A and B: Posterior pole toxocara granuloma, epiretinal membranes and vitreoretinal tractions in a 12-year- old female patient – preoperative appearance; B. Postoperative (Pars plana vitrectomy) appearance demonstrating relief of vitreoretinal tractions

Figure 4: Peripheral toxocara granuloma, retinal pigment epithelial atrophy and hyperplasia in a 36-year-old male patient

fold of the retina extending from the peripheral granuloma to the optic disc (Figure 5). Endophthalmitis may present with severe anterior (hypopyon) and posterior

Figure 5: Vitreoretinal membranes, retinal fold in a 24-year- old female patient with a peripheral toxocara granuloma

inflammation or may have the form of chronic endophthalmitis.

Other less common presentations of ocular toxocariasis are optic neuritis, neuroretinitis and mobile living larva in the eye.

The complications include macular heterotopia, epiretinal membranes, cataract, secondary glaucoma, tractional retinal detachment, detachment of the ciliary body and anterior choroid with hypotony, phthisis bulbi and neovascular membranes9 (Figure 6).

Differential diagnosis of ocular toxocariasis includes retinoblastoma, Coat’s disease, persistent hyperplastic primary vitreous, familial exudative vitreoretinopathy, retinopathy of prematurity, toxoplasmosis, pars planitis and endogenous endophthalmitis.

Figure 6: Retinal detachment in a 37-year-old female patient with a peripheral toxocara granuloma

IMAGING TECHNIQUES

Ultrasonography (USG) is helpful in establishing diagnosis of ocular toxocariasis.

The most characteristic findings are: highly reflective peripheral mass (mostly in the temporal periphery), pseudocystic transformation of the peripheral vitreous, vitreous membranes or retinal fold extending from the mass to the posterior pole and tractional retinal detachment12 (Figures 7A, B and 8). USG is also useful in differentiating toxocara granuloma from retinoblastoma (calcification).

High-frequency ultrasound biomicroscopy (UBM) may also contribute significant information in the assessment of inflammatory lesions in ocular toxocariasis, especially in patients with opaque media or hypotony. This technique was shown to generate pseudocystic images of the vitreous found in most of the patients, representing a highly sensitive finding although not very specific13,14 (Figure 9).

Computed tomography (CT) scans may reveal calcification in retinoblastoma, but are not useful in discreminating toxocara granuloma and noncalcified retinoblastoma. Magnetic resonance imagings (MRI) demonstrate that toxocara lesions are hyperintense in

Figures 7A and B: A. Posterior pole toxocara granuloma involving macula, epiretinal membranes in a 29-year-old female patient (diagnosed as toxocariasis at the age of 16); B. Ultrasound image of this patient

Figure 8: Ultrasound image of peripheral toxocara granuloma and vitreoretinal tractions in a 6-year-old female patient

T2-weighted scans (unlike retinoblastoma) and are hyperintense in T1 and proton-weighted scans (like retinoblastoma).15

Figure 9: Typical pseudocystic degeneration of vitreous seen by UBM in a case of ocular toxocariasis

In optical coherence tomography (OCT) images posterior pole granuloma may appear as a highly reflective mass protruding above the retinal pigment epithelium.

TREATMENT AND PROGNOSIS

Peripheral or posterior pole granuloma with no or minimal inflammation may not require treatment. In cases with severe inflammation systemic or periocular corticosteroids should be administered.16 The use of anthelmintic drugs (thiabendazole, albendazole, diethylcarbamazine) in ocular toxocariasis is still controversial.17 It is generally advised to combine them with systemic or periocular corticosteroids.

Vitrectomy is recommended in severe inflammation non-responding to medical therapy and in the treatment of complications such as epiretinal membranes, vitreoretinal traction and retinal detachment.18 Prognosis depends on the age of presentation, location of toxocara lesions and subsequent complications. In cases with peripheral granuloma with no inflammation or vitreoretinal tractions, prognosis may be good, whereas presence of posterior pole granuloma with macular involvement or severe complications such as retinal detachment may lead to

permanent loss of vision.

KEY POINTS

1.Ingesting the eggs of Toxocara causes Toxocariasis.

2.Common clinical presentations include intraocular granuloma formation in posterior pole or periphery and endophthalmitis like picture

3.Death of the larva leads to severe intraocular inflammation.

4.The first line of treatment is use of systemic or periocular corticosteroids.

5.Vitreous surgery is useful to manage the secondary effects of the disease.

REFERENCES

1.Molk R. Ocular toxocariasis: a review of the literature. Ann Ophthalmol 1983;15:216-31.

2.BenEzra D. Toxocara. In: BenEzra D (Ed). Ocular Inflammation. Basic and Clinical Concepts. Martin Dunitz, 1999.

3.Ellis GS, Pakalnis VA, Worley G, et al. Toxocara canis infestation. Clinical and epidemiological associations with seropositivity in kindergarten children. Ophthalmology 1986;93:1032-7.

4.Taylor MR. The epidemiology of ocular toxocariasis. J Helminthol 2001;75:109-18.

5.Shields JA. Ocular toxocariasis: a review. Surv Ophthalmol 1984;28:361-81.

6.Brown DH. Ocular toxocariasis II : clinical review. J Pediatr Ophthalmol 1970;7:182-91.

7.Upadhyay MP, Rai NC. Toxocara granuloma of the retina. J J Ophthalmol 1980;24:278-81.

8.Gonvers M, Mermoud A, Uffer S, Herbort CP, Bovey E. Toxocariasis in a 30 year old patient. Klin Mbl Augenheilk 1992;200:522-4.

9.Monshizadeh R, Ashrafzadeh MT, Rumelt S. Choroidalneovascular membrane: a late complication of inactive toxocara chorioretinitis. Retina 2000;20:219-20.

10.Magnaval JF, Malard L, Morassin B, Fabre R. Immunodiagnosis of ocular toxocariasis using Western-blot for the detection of specific anti-Toxocara IgG and CAP for the measurement of specific anti-Toxocara IgE. J Helminthol 2002;76:335-9.

11.Feldberg NT, Shields JA, Fed JL. Antibody to toxocara canis in the aqueous humor. Arch Ophthalmol 1981;99:1563-4.

12.Wan WL, Cano MR, Pince KJ, et al. Echographic characteristics of ocular toxocariasis. Ophthalmology 1991;98:28-32.

13.Tran VT, Lumbroso L, LeHoang P, Herbort CP. Ultrasound biomicroscopy in peripheral retinovitreal toxocariasis. Am J Ophthalmol 1999;127:607-9.

14.Tran VT, LeHoang P, Herbort CP. Value of high-frequency ultrasound biomicroscopy in uveitis. Eye 2001;15:23-30.

15.Mafee MF, Goldberg MF, Cohen SB, et al. Magnetic resonance imaging versus computed tomography of leukocoric eyes and use of in vitro proton magnetic resonance spectroscopy of retinoblastoma. Ophthalmology 1989;965-75.

16.Dinning WJ, Gillespie SH, Cooling RJ, et al. Toxocariasis: a practical approach to management of ocular disease. Eye 1988;2:580-2.

17.Barisani-Asenbauer T, Maca SM Hanff W, et al. Treatment of ocular toxocariasis with albendazole. J Ocul Pharmacol Therp 2001;17:287-94.

18.Belmont JB, Irvine A, Benson W, et al. Vitrectomy in ocular toxocariasis. Arch Ophthalmol 1982;100:1912-15.

INTRODUCTION

Rickettsioses are zoonoses due to obligate intracellular small gram-negative bacteria. Most of them are transmitted to humans by the bite of contaminated arthropods, such as ticks. Rickettsial agents are classified into three major categories: the spotted fever group, the typhus group, and the scrub typhus.1,2

The spotted fever group includes Mediterranean spotted fever (MSF), Rocky Mountain spotted fever (RMSF), and numerous other rickettsioses. MSF, also called “boutonneuse” fever or tick-borne rickettsiosis, which is caused by the organism Rickettsia (R.) conorii, is prevalent in Mediterranean countries and Central Asia, including India. RMSF, which is caused by R. rickettsii, is endemic in parts of North, Central, and South America, especially in the south-eastern and south-central United States. Epidemic typhus, which is caused by the organism R. prowazekii, is usually encountered in areas of crowded population with poor hygiene conditions, as occurs during wars and natural disasters. Murine typhus, which is caused by R. typhi, is found worldwide in warm-climate countries. Scrub typhus, which is caused by Orientia tsutsugamushi, is a zoonosis found in the Far East.1,2

For most of the organisms of the spotted fever and typhus groups, the target cells are the endothelial cells of blood vessels. Invasion of vascular endothelial cells by the organism causes endothelial injury and tissue

necrosis, with subsequent development of a host mononuclear-cell tissue response and stimulation of coagulation process, resulting in a systemic edematous and occlusive vasculitis.1

SYSTEMIC FEATURES OF RICKETTSIOSES

A rickettsial disease should be suspected, during spring or summer, in the presence of the triad of high fever, headache and general malaise, and skin rash (Figure 1) in a patient living in or traveling back from a region endemic for rickettsioses. A local skin lesion, termed

Figure 1: A maculopapular skin rash in a patient with Mediterranean spotted fever

“tache noire” (black spot) may develop at the site of arthropod bite in MSF and several other rickettsioses (Figure 2). A history of outdoor activities, occupational exposure, or tick attachment is frequent.1,2 Prognosis of systemic infection is good in most cases. However, severe complications and death may occur.

OPHTHALMIC MANIFESTATIONS OF

RICKETTSIOSES

Ocular involvement is common in patients with rickettsiosis, but since it is frequently asymptomatic and self-limited, it may be easily overlooked. However, rickettsial ocular disease may be associated with ocular complaints, such as decreased vision, scotoma, floaters, or redness. Retinitis, retinal vascular involvement, and optic disc changes are the most common ocular findings, but numerous other manifestations may occur.3-36

ADNEXAL AND ANTERIOR SEGMENT MANIFESTATIONS

Contamination of the conjunctiva by a spurt of tick blood, resulting in unilateral conjunctivitis, has been implicated as the portal of entry for R. rickettsii, as well as R. conorii infection.3,5 Bilateral conjunctivitis has been described in association with MSF as well as RMSF.4,26 Conjunctival petechiae and subconjunctival haemorrhages have also been described.6 A case of ameboid type of corneal ulceration similar to herpetic epithelial

Figure 2: “Tache noire” in the armpit of a patient with Mediterranean spotted fever. Note also the presence of a skin rash

keratitis has been associated with MSF. The lesion responded readily to the use of topical tetracycline ointment.7

Non-granulomatous anterior uveitis without or with associated posterior segment involvement has been described with rickettsioses.3,8,9,24 An iris nodule was reported in association with RMSF.31

RETINOCHOROIDAL INVOLVEMENT

Retinochoroidal involvement is common in patients with rickettsioses. In a recent prospective study, more than 80% of patients with acute MSF examined by ophthalmoscopy and fluorescein angiography had chorioretinal involvement, which was frequently asymptomatic.24 Because the diagnosis of chorioretinal involvement in rickettsioses may be easily overlooked, a careful dilated funduscopic examination, complemented with fluorescein angiography in selected cases, is recommended. Retinitis and retinal vascular changes are the most common and typical manifestations of rickettsial infection, but numerous other findings may be encountered.

Retinitis

It is observed in at least 30% of patients with acute MSF.24 It presents in the form of white retinal lesions, typically adjacent to retinal vessels. These lesions may vary in number (from 1 to more than 5 per eye), size (very small to large), topography (posterior fundus or periphery), and retinal layer location (superficial or full-thickness involvement) (Figures 3-6).

An associated mild or moderate vitreous inflammation is commonly observed. Fluorescein angiography showed early hypofluorescence and late staining of large acute white retinal lesions and isofluorescence or moderate hypofluorescence of small active retinal lesions throughout the whole phase of dye transit. 24

There are reports of multiple small white retinal lesions in other rickettsioses, including RMSF, Queensland tick typhus, and murine typhus.27-30, 33, 34 Some small white retinal lesions in posterior pole might be interpreted as cotton-wool ischaemic spots, with corresponding focal areas of capillary nonperfusion on fluorescein angiography.23,29 Multiple retinal lesions similar to those seen in multiple evanescent white dot syndrome (MEWDS) have been reported.15,35

Figures 3A-C: An 18-year-old woman with MSF complained of blurred vision in the right eye. Visual acuity was 20/25 (both eyes). (A) Colour fundus photograph of the right eye shows a nasal juxtavascular white retinal lesion with associated serous retinal detachment and a macular star. Fluorescein angiography shows early hypofluorescence (B) and late staining (C) of the retinal lesion, retinal vascular leakage, and optic disc hyperfluorescence (Figure 3A reproduced from Figure 3 Ophthalmology 2004;111:529-34)

Figures 4A and B: This patient with MSF has a juxtavascular white retinal lesion associated with retinal haemorrhages in the superior midperiphery (A, arrow) and a focal vascular sheathing in the inferior periphery (B, arrow)

Figures 5A and B: This patient with MSF without ocular complaints has small white retinal lesions in posterior pole of the left eye (arrows) associated with a retinal haemorrhage (A).

(B) Midphase fluorescein angiogram shows isofluorescence of the retinal lesions

The pathogenesis of rickettsial retinitis remains speculative. White retinal lesions could result from intraretinal rickettsial multiplication. Alternatively, immune response to bacteraemia could lead immune complexes and inflammatory cells to form white infiltrates through deposition in retinal vessels.24

Retinal Vascular Involvement

Since the physiopathologic basis for rickettsial infectious diseases is vasculitic, one may expect retinal vascular involvement to be common. In a recent study, nearly half of patients with acute MSF had retinal vascular changes.24 Numerous retinal vascular lesions have been described in association with rickettsioses. They included focal or diffuse vascular sheathing, vascular leakage, intraretinal, white-centered, or subretinal haemorrhages, and retinal vascular occlusions associated with transient or permanent visual loss, including branch and central artery occlusion, and branch retinal vein occlusion or subocclusion16-18,23,24,36 (Figures 3-7).

Other Retinal Changes

They include serous retinal detachment, cystoid macular oedema, and macular star24,32 (Figure 3A).

Endogenous Endophthalmitis

A case of endogenous endophthalmitis caused by R. conorii was reported recently.19

Vitreous cultures remained negative, but the ocular condition cleared after intravitreal chloramphenicol injection and systemic doxycycline.

Choroidal Involvement

A subclinical choroidal involvement in the form of multiple dark dots on fluorescein angiography was observed in more than 15% of patients with MSF.24

The principal finding on ICG angiography is the presence of small hypofluorescent spots (>80%) in the intermediate and late phases (Figure 8). These lesions probably correspond to focal areas of ischaemic choroidal vasculitis. Other findings include areas of hyperfluorescence, choroidal vascular filling defect, and choroidal vascular staining (Personal unpublished data).

NEURO-OPHTHALMIC MANIFESTATIONS

Optic nerve involvement, with or without visual loss, has been described in association with rickettsial infection. It included optic disc oedema, optic disc staining, optic neuritis, neuroretinitis, and ischaemic optic neuropathy.20-25, 32 Third and six cranial nerve palsies have also been reported.

Figures 6A-C: This 30-year-old woman with MSF complained of a paracentral scotoma in the left eye. Visual acuity was 20/ 20 in both eyes. (A) Colour fundus photograph of the right eye shows 4 small white retinal lesions in the inferior periphery. Colour fundus photograph (B) and midphase fluorescein angiogram (C) of the left eye shows superotemporal branch retinal artery occlusion sparing the fovea. Note the presence of 2 small white retinal lesions nasal to the optic disc on fundus photograph of the left eye (Figure 6B reproduced from Figure 2B from Ophthalmology 2004;111:529-34)

DIAGNOSIS

Diagnosis of rickettsial infection usually based on clinical features and epidemiologic data is confirmed by positive indirect immunofluorescent antibody test results. Positive serologic criteria usually include either initial high antibody titre or a fourfold rise of the titre in the convalescent serum. Case confirmation with serology might take 2 to 3 weeks. Other laboratory tests, such as serologic testing using western blot or detection of rickettsiae in blood or tissue using polymerase chain reaction, may be helpful in selected cases.

Ocular examination, revealing frequently abnormal, fairly typical findings is helplful in diagnosing a rickettsial disease, particularly in incomplete and atypical systemic presentation, while serologic testing is pending.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of rickettsiosis includes numerous systemic infectious and noninfectious diseases manifesting with febrile illness, such as typhoid fever, measles, rubella, enteroviral infection, meningococcemia, disseminated gonococcal infection, secondary syphilis, leptospirosis, cat scratch disease, infectious mononucleosis, arbovirus infection, Kawasaki disease, Behçet´s disease and other systemic vasculitic disorders, idiopathic thrombocytopenic purpura, and drug reaction.

Other important causes of retinitis and vasculitis such as toxoplasmosis and sarcoidosis should also be considered.

TREATMENT

Early treatment is critical to outcome and must be started on the basis of clinical diagnosis. Doxycycline (100 mg every 12 hours for 7 to 10 days) is the drug of choice for the treatment of rickettsial diseases. Antibiotic treatment may be terminated 48 hours after the patient is afebrile. Other tetracyclines (25-50 mg/kg/ day), chloramphenicol (50-75 mg/kg/day) in four divided doses, and fluoroquinolones are also effective. Both tetracyclines and chloramphenicol have potential significant adverse effects, especially in children. Macrolides, including clarithromycin, azithromycin, and particularly josamycin can be used as alternative therapy in children and pregnant women.1

Figure 7: This patient with MSF has white-centered haemorrhages (arrows)

Fluoroquinolones, because of their good ocular penetration, might be more effective than doxycycline in the treatment of intraocular rickettsial disease. Additional therapeutic agents may be required for ocular disease: topical antibiotic for conjunctivitis or keratitis, topical steroids and mydriatic drops for anterior uveitis, systemic steroids for severe ophthalmic involvement, such as extensive retinitis threatening the macula or optic disc, serous retinal detachment, macular oedema, retinal vascular occlusion, severe vitritis, and optic neuropathy, and anticoagulant agents for retinal vascular occlusions. The role of antibiotic therapy, as well as that of oral steroids, on the course of posterior segment involvement, remains unknown.

Figure 8: Late phase indocyanine green angiogram of the left eye of a patient with MSF without ocular complaints show small well-delineated hypofluorescent lesions, without corresponding abnormalities on clinical examination or fluorescein angiography

The effect of anticoagulants on the course of retinal occlusive complications is also unclear.18

Prevention is the mainstay for control of rickettsial diseases: personal protection against tick bites in endemic areas (repellents, protective clothing, avoidance of dogs, detection and removal of an attached tick), improvement of sanitary conditions including the control of rat reservoirs and of flea or lice vectors.

EVOLUTION AND PROGNOSIS

Although prognosis of systemic infection is good in most cases, rickettsioses may be severe and potentially lethal, and should be treated accordingly.

Ophthalmic manifestations of rickettsioses have a self-limited evolution in most patients, disappearing between the 3rd and 10th week after the first examination. All inner white retinal lesions clear without causing scarring. Retinal pigment epithelium (RPE) changes develop in eyes with resolved full-thickness white retinal lesions. Retinal neovascularisation developed in one patient after resolution of retinitis six months after initial presentation.24 Visual acuity returns to baseline in most patients. Persistent decreased vision may occur due to retinal changes secondary to macular oedema or serous retinal detachment, retinal artery or vein occlusion, foveal chorioretinal scar, or optic neuropathy.

KEY POINTS

•The best diagnostic tool of rickettsial infection relies on a high index of suspicion in the presence of the triad of high fever, headache and general malaise, and skin rash in a patient living in or traveling back from a region endemic for rickettsioses. The sooner the clinical diagnosis is made and appropriate treatment is begun, the better the prognosis.

•Ocular involvement in rickettsioses is common, but is frequently asymptomatic and easily overlooked.

•Retinitis presenting as small or large white retinal lesions associated with mild or moderate vitritis and retinal vascular lesions are the most common and typical findings.

•A careful dilated fundus examination, complemented with fluorescein angiography in selected cases, is recommended in patients with clinically suspected rickettsial disease. It may be helpful in establishing an early diagnosis, especially in incomplete and atypical clinical presentations.

•Rickettsial infection should be considered in the differential diagnosis of retinitis, retinal vasculitis, or any

intraocular inflammatory condition in a patient living in or returning from a specific endemic area, especially during spring or summer.

•A subclinical retinal and choroidal vascular involvement visible only on fluorescein or ICG angiography is common.

•The differential diagnosis of rickettsial retinitis includes many conditions, mainly acquired ocular toxoplasmosis (single large white retinal lesion) and cat scratch disease (small white retinal lesions, retinal vascular involvement, optic disc oedema, macular star).

•Doxycycline is the drug of choice in the treatment of rickettsioses, but prevention is the mainstay of rickettsial infection control. Fluoroquinolones, because of their good ocular penetration, might be a better therapeutic option for the treatment of intraocular involvement. Corticosteroid therapy may be required in addition to antibiotic treatment.

REFERENCES

1.Parola P, Raoult D. Rickettsioses éruptives. EMC (Elsevier Paris) Maladies infectieuses, 8-037-I-20, 1998, 24p.

2.Mc Dade JE. Rickettsial diseases. In: Hausler WJ, Sussman M, (Eds). Topley and Wilson’s Microbiology and Microbial Infections, (9th edn), London: Arnold 1998; 3:995-1011.

3.Bazin R. Rickettsial diseases. In: Foster CS, Vitale A, (Eds). Diagnosis and Treatment of Uveitis. Philadelphia: WB Saunders Company 2002;297-304.

4.Martin Fer-Fan A, Juarez C, Calbo F, Porras J, Diaz M, Bermudez F. Estudio clinico-epidemiologico de 164 casos de fiebre botonosa. Rev Clin Esp 1985;176:333-9.

5.Pinna A, Sotgiu M, Carta F, Zanetti S, Fadda G. Oculoglandular syndrome in mediterranean spotted fever acquired through the eye. Br J Ophthalmol 1997;81:172.

6.François J. Rickettsiae in ophthalmology. Ophthalmologica 1968;156:459-72.

7.Alio J, Ruiz-Beltran R, Herrera I, Artola A, Ruiz-Moreno JM. Rickettsial keratitis in a case of Mediterranean spotted fever. Eur J Ophthalmol 1992;2:41-3.

8.Bloch-Michel E, Ginnepain MT, Edlinger E, Schmidt A, Herman D. Fièvre bou-tonneuse méditerranéenne : à propos de la physiopathologie des manifestations uvéales. Bull Mém Soc Fr Ophtalmol 1983;95:566-70.

9.Rizo AE, Muniz O, Auladell C, Miranda ML. A case of bilateral uveitis secondary to Mediterranean Spotted Fever. Clin Inf Diseases 1992;14:624-5.

10.Pinna A, Sechi LA, Serru A, et al. Endogenous panuveitis in a patient with Rickettsia conorii infection. Acta Ophthalmol Scand 2000;78:608-9.

11.Fontaine M, Saraux H, Ganem J. Rickettsioses et uvéites. Bull Mém Soc Fr Ophtalmol 1960;73:491-9.

12.Lebas M, Bernaerts-Lebas M. Rickettsioses et affections oculaires. Bull Soc Belge Ophthalmol 1963;135:937-56.

13.Restat S, Lenoble P, Nasica X, et al. La fièvre boutonneuse méditerranéenne : A propos d’un cas. J Fr Ophtalmol 1999;22:554-61.

14.Blazquez JC, Serrano C, De Teresa L, Priego M. Retinal vasculitis secondary to Mediterranean exanthemathous fever. Enfermedades infecciosas 2000;5:249-50.

15.Esgin H, Akata F. Bilateral multiple retinal hyperfluorescent dots in a presumed Rickettsia conorii infection. Retina 2001;21:535-7.

16.Paufique L, Bonnet M, et al. Thromboses vasculaires rétiniennes et rickettsioses. Bull Soc Ophtalmol Fr 1964;64:410-5.

17.Verdot S, Estavoyer JM, Prost F, Montard M. Atteinte oculaire en phase aiguë de fièvre boutonneuse méditerranéenne. Bull Soc Ophtalmol Fr 1986;86:429-31.

18.Adan A, Lopez-Sorra A, Moser C, Coca A. Use of steroids and heparin to treat retinal arterial occlusion in Mediterranean spotted fever. J Infect Dis 1998;158:1139-40.

19.Mendivil A, Cuartero V. Endogenous endophthalmitis caused by Rickettsia conorii. Acta Ophthalmol Scand 1998;76:121-2.

20.Bronner A, Payeur G. Hemorrhagic papillitis and rickettsiosis. Bull Soc Ophtalmol Fr 1973;73:355-8.

21.Castanet J, Costet C, Dubois D, et al. Neuropathie optique au cours d’une fièvre boutonneuse méditerranéenne. Presse Med 1988;17:439-40.

22.Granel B, Serratrice J, Rey J, Conrath J, Disdier P, Weiller PJ. Impaired visual acuity in Mediterranean boutonneuse fever. Presse Med 2001;30:859.

23.Alio J, Ruiz-Beltran R, Herrero-Herrero JI, Hernandez E. Retinal manifestations of Mediterranean spotted fever. Ophthalmologica 1987;195:31-7.

24.Khairallah M, Ladjimi A, Chakroun M, et al. Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 2004;111(3):529-34.

25.Khairallah M, Zaouali S, Ben Yahia S, Ladjimi A, Messaoud R, Jenzeri S, Attia S. Anterior ischemic optic neuropathy associated with Rickettsia conorii infection. J Neuro-ophthalmol 2005;25:212-4.

26.Helmick CG, Bernard KW, D’Angelo LJ. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis 1984;150:480-8.

27.Raab EL, Leopold IH, Hodes HL. Retinopathy in Rocky Mountain spotted fever. Am J Ophthalmol 1969;68:42-6.

28.Presley GD. Fundus changes in Rocky Mountain spotted fever. Am J Ophthalmol 1969;67:263-7.

29.Smith TW, Burton TC. The retinal manifestations of Rocky Mountain spotted fever. Am J Ophthalmol 1977;84:259-62.

30.Duffey RJ, Hammer ME. The ocular manifestations of Rocky Mountain spotted fever. Ann Ophthalmol 1987;19:301-6.

31.Cherubini TD, Spaeth GL. Anterior nongranulomatous uveitis associated with Rocky Mountain spotted fever. First report of a case. Arch Ophthalmol 1969;81:363-5.

32.Vaphiades MS. Rocky Mountain Spotted Fever as a cause of macular star figure. J Neuroophthalmol 2003;23:276-8.

33.Lukas JR, Egger S, Parschalk B, Stur M. Bilateral small retinal infiltrates during rickettsial infection. Br J Ophthalmol 1998; 82:1217-8.

34.Hudson HL, Thach AB, Lopez PF. Retinal manifestations of acute murine typhus. Int Ophthalmol 1997;21:121-6.

35.Lu TM, Kuo BI, Chung YM, Liu CY. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis 1997;296:632-3.

36.Nagaki Y, Hayasaka S, Kadoi C, Matsumoto M, Sakagami T. Branch retinal vein occlusion in the right eye and retinal hemorrhage in the left eye in a patient with classical tsutsugamushi disease. Jpn J Ophthalmol 2001;45:108-10.

INTRODUCTION

The West Nile virus (WNV), first isolated in 1937 in the West Nile district of Uganda, is an enveloped single-stranded RNA flavivirus. It is a member of the Japanese encephalitis virus serocomplex, which includes Japanese encephalitis virus, Saint Louis encephalitis virus, Murray Valley encephalitis virus, and Kunjin virus.1 The virus is widely distributed in Africa, Europe, Australia, and Asia, and, since 1999, it has spread rapidly throughout the Western hemisphere, including the United States, Canada, Mexico, and the Caribbean and into parts of Central and South America.2 West Nile virus infection is a zoonotic disease most often transmitted to human by an

infected Culex mosquito vector with wild birds serving as its reservoir. The disease has been reported to occur anytime between July and December, with a peak onset in late summer. Other modes of transmission have recently been recognised, including blood transfusion, organ transplantation, transplacental transmission, laboratory transmission, and breast feeding.3

SYSTEMIC MANIFESTATIONS

OF WNV INFECTION

The incubation period of WNV ranges from 3 to 14 days. About 80% of human infections are apparently asymptomatic. Only approximately 20% of persons