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

Figure 6: Serpiginous choroiditis. Most probably caused by a vasculitis of the choriocapillaris which is possibly primary. The severity of the involvement leading to irreversible atrophy could speak for a process directed directly against the choriocapillaris vessel wall. No histology is available to settle the question

Figure 7: Idiopathic retinitis vasculitis, aneurysm and neuroretinitis (IRVAN)

an unusual ocular involvement, that responded well to the administration of corticosteroids and was not due to ocular ischaemia.12 In their series of 9 patients Biswas et al showed that scleritis with peripheral corneal ulceration peripheral ulcerative keratitis (PUK) was the most frequent ocular sign in contrast to the predominant orbital involvement usually reported in the literature.13 Two case report articles on ocular involvement in Churg-Strauss syndrome (CSS) stress the two main types of ocular lesions, orbital involvement in the form

of pseudotumours, presenting also rarely as a myositis that is usually ANCA-negative14 and the ischaemicvasculitic type, usually ANCA-positive with serious consequences on the retina and visual function.15

SECONDARY VASCULITIS OR INFLAMMATORY VASCULOPATHY LIMITED TO THE EYE

Birdshot chorioretinopathy is an ocular vasculitis involving retinal, choroidal and optic disc vessels for which no systemic involvement has been found so far despite a very strong close to 100% association with the HLA-A 29 major histocompatibility antigen. Recently the first autopsy case has shown that the choroidal inflammation is characterised by granulomatous foci and choroidal vasculitis indicating that the vasculopathy in birdshot chorioretinopathy is secondary to a granulomatous inflammation.16

An angiographic study using fluorescein and indocyanine green angiography has shown that retinal vasculitis and choroidal inflammation occur and develop independently from each other.17 Choroidal disease is responding well to corticosteroid and immunosuppressive therapy, whereas retinal involvement is more resistant to therapy and is responsible for the severe functional impairment occurring in some of the cases.17 Eale’s disease, often also called tuberculoprotein hypersensitivity vasculitis because a hyperpositive tuberculin skin test present in these patients, includes peripheral retinal periphlebitis, nonperfusion and recurrent vitreous haemorrhages due to neovascularisation. A recent study showed that reactive nitrogen species (RNS) and reactive oxygen species (ROS) were elevated in Eale’s patients indicating that free radicals are involved in mediating tissue damage.18 Sympathetic ophthalmia is a bilateral granulomatous inflammation thought to be caused by a sensitisation of the immune system to secluded ocular antigens after a penetrating eye injury. The disease causes a granulomatous inflammation in the choroid and a secondary choroidal vasculitis and is limited to the eye. A recent report on sympathetic ophthalmia associated with cerebral vasculitis seems to indicate, if this confirmed in future, that the inflammation can have a systemic expression in some cases.19 In all these conditions vascular lesions are secondary to another inflammatory process than direct vessel

wall involvement and these conditions are or seem to be limited to the eye.

SECONDARY SYSTEMIC VASCULITIDES INVOLVING THE EYE AND ADNEXAE

Susac’s syndrome is a microangiopathy involving the arterioles of the brain, the retina and the cochlea and is clinically presenting with subacute encephalopathy, branch retinal artery occlusion and sensorineural hearing loss. Primary vessel inflammation has not been proven and we classified the disease in the secondary systemic vasculitis until proven otherwise. A recent series of four patients with Susac’s syndrome preceded by an editorial by John Susac, gives a complete review of this underdiagnosed disease with good MRI images and histopathology of arteriolar lesions.20,21

A prominent cause of a secondary systemic vasculitis often involving the eye is Behçet’s disease that manifests itself by retinal vasculitis (Figure 4). The disease also causes vasculitis in the choroid but only at the onset of intraocular inflammation, and in any other ocular location including rarely the episclera (Figure 8). Another prominent inflammatory situation causing intraocular vasculitis both in the retina and the choroïd is sarcoidosis (Figures 9A and B).

A multitude of ocular sites can be involved by the vasculitis associated with inflammatory bowel diseases (IBD). Episcleritis and scleritis are associated with IBD in up to 29 and 18% respectively. Uveitis is usually nongranulomatous and mostly associated with the presence of the HLA-B27 major histocompatibility antigen. PUK can be present by itself but can also be

Figure 8: Episcleritis in a patient with Behçet’s disease and Behçet’s uveitis

seen together with scleritis. Orbital pseudotumour and optic neuropathy have also been described as was retinal vasculitis.22 Ocular involvement in association with IBD has been reviewed exhaustively in a recent review.22 Similar review work has been done to identify the lesions shared by the kidney and the eye in primary and secondary vasculitic processi.23 Numerous infectious causes are at the origin of articles dealing with ocular vasculitis associated with infectious causes have been published but we will cite only a few articles on emerging agents or newly recognised pathology. Rickettsial diseases are known to cause retinal vasculitis. A recent series of 30 patients with Mediterranean spotted fever caused by Rickettsia conorii showed that about half of the patients had signs of retinal vasculitis on clinical examination or by fluorescein angiography and this aetiology should be considered in endemic areas24 (see chapter 33A).

Human T-cell lymphotropic virus type 1 (HTLV- 1), an RNA retrovirus endemic in Japan, the Caribean islands and parts of Central Africa and South America causing adult T-cell lymphoma (ATL), HTLV-1 associated myelopathy and tropical spastic paresis (HAM/TSP). Ocular inflammation associated was first described by Mochizuki et al in 1992 and includes granulomatous and non-granulomatous anterior uveitis, intermediate uveitis retinochoroidal lesions and retinal vasculitis.25 Buggage recently published a very complete review article on the ocular involvement and ocular vasculitis in HTLV-1 infection.26

The West Nile virus (WNV) is one of emerging infectious agents causing retinal and choroidal vasculitis. It is a single-stranded RNA flavivirus belonging to the Japanese encephalitis virus serocomplex. It was first isolated in 1937 in the West Nile district of Uganda and is transmitted by a mosquito vector with wild birds serving as its reservoir and is distributed extensively throughout Africa, Asia, the Middle East, Europe, and North America. About 20% of infected persons are symptomatic and present a flulike illness developing into meningitis or encephalitis in 1% of cases. Almost 80% of patients have posterior segment involvement consisting of 20 to 50 roundish lesions per eye with a size from 100 to 1500 μm and a linear disposition. Associated retinal vascular changes include intraretinal haemorrhages, white-centered haemorrhages, focal vascular sheathing, and retinal

vascular leakage. Thanks to the work of a Tunisian group that published the largest series so far on ocular involvement due to West Nile virus infection and performed a prospective study during the last zoonose in their country, the clinical picture has been well established.27 Occlusive retinal vasculitis has been described in association with West Nile virus infection28 (see chapter 33B).

CONCLUSION

Vasculitic involvement of the eye should not be reduced to retinal vasculitis alone any longer. The emerging term of ocular vasculitis should apply to all ocular and periocular lesions caused by a vasculitic process including episcleritis, scleritis and PUK, retinal vasculitis, choroidal vasculitis, optic nerve vasculitis, as well as orbital and adnexal lesions. The ophthalmologist should try to classify ocular lesions suspected to be of vasculitic origin within the new classification presented here and derived from the universally accepted classification of systemic vasculitis. This will allow a multidisciplinary approach of the great proportion of cases of ocular vasculitis that are part of a systemic disease.

KEY POINTS

•New investigational techniques to detect vasculitis in ocular structures other than the retina have been developed.

•Appraisal of vasculitis in other sectors than the retina alone contributed to the development of the global concept of ocular vasculitis.

•Importance to promote a comprehensive and global classification of ocular vasculitis compatible with the concepts accepted for systemic vasculitis in order to contribute to its multidisciplinary approach.

REFERENCES

1.Herbort CP, Guex-Crosier Y, LeHoang P. Schematic interpretation of indocyanine green angiography Ophthalmology 1994;2:169-76.

2.Herbort CP, Bodaghi B, LeHoang P. Angiographie au vert d’indocyanine au cours des maladies inflammatoires : principes, interpretation schématique, sémiologie et intérêt clinique. J Fr Ophtalmol 2001;24:423-47.

3.Cimino L, Auer C, Herbort CP. Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies. Ocular Immunologie and Inflammation 2000;8:275-83.

4.Bouchenaki N, Cimino L, Auer C, Tran VT, Herbort CP. Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography. Klin Monatsbl Augenheilkd 2002;219:243-9.

5.Herbort CP, Cimino L, Abu El Asrar A. Ocular vasculitis: a multidisciplinary approach. Curr. Opin Rheumatol 2005; 17:25-33.

6.Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337:1512-23.

7.Perez VL, Chavala SH, Ahmed M, et al. Ocular manifestations and concepts of systemic vasculitides. Surv Ophthalmol 2004;49:399-418.

8.Herbort CP. Choroiditis, general considerations and classification. In: Pleyer U, Mondino B (Eds). Essentials in Ophthalmology: Uveitis and Immunological Disorders. Berlin, Heidelberg, New York: Springer 2004;202-8.

9.Cimino L, Mantovani A, Herbort CP. Primary inflammatory choriocapillaropathies. In: Pleyer U, Mondino B (Eds). Essentials in Ophthalmology: Uveitis and Immunological Disorders. Berlin, Heidelberg, New York: Springer; 2004;209-31.

10.Bouchenaki N, Herbort CP. Stromal choroiditis. In: Pleyer U, Mondino B (Eds). Essentials in Ophthalmology: Uveitis and Immunological Disorders. Berlin, Heidelberg, New York: Springer; 2004;234-53.

11.Abu El-Asrar AM, Jestaneiah S, Al-Serhani AM. Regression of aneurismal dilatations in a case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) associated with allergic fungal sinusitis. Eye 2004;18:197201.

12.McDonald MA, Ojaimi E, Favilla I. Anterior uveitis in a child with Takayasu’s arteritis. Clin Experiment Ophthalmol 2004;32:336-9.

13.Biswas J, Babu K, Gopal L, Krishnakumar S, Suresh S, Ramakrishnan S. Ocular manifestations of Wegener’s granulomatosis. Indian J Ophthalmol 2003;51:217-23.

14.Billing K, Malhotra R, Selva D, Dodd T. Orbital myositis in Churg-Strauss Syndrome. Arch Ophthalmol 2004; 122:393-6.

15.Partal A, Moshfeghi DM, Alcorn D. Churg-Strauss syndrome in a child: retina and optic nerve findings. Br J Ophthalmol 2004;88:971-2.

16.Gaudio PA, Kaye DB, Brooks Crawford J. Histopathology of birdshot retinochoroidopathy. Br J Ophthalmol 2002; 86:1439-41.

17.Herbort CP, Probst K, Cimino L, Tran VT. Differential inflammatory involvement in retina and choroids in birdshot chorioretinopathy. Klin Monatsbl Augenheilkd 2004;221:351-6.

18.Rajesh M, Sulochana KN, Punitham R, Biswas J, Lakshimi S, Ramakrishnan S. Involvement of oxidative and nitrosactive stress in promoting retinal vasculitis in patients with Eale’s disease. Clinical Biochemistry 2003;36:377-85.

19.Kadayifçilar S, Irkeç M, Eldem B. Sympathetic ophthalmia associated with ocular and cerebral vasculitis : an angiographic and radiologic study. Eur J Ophthalmol 2003;13:584-7.

20.Susac J. Susac’s syndrome. Am J Neuroradiol 2004;25:351- 2.

21.Do TH, Fisch C, Evoy F. Susac syndrome: report of 4 cases and review of the literature. Am J Neuroradiol 2004; 25:382-8.

22.Ghanchi FD, Rembacken BJ. Inflammatory bowel disease and the Eye. Surv Ophthalmol 2003;48:663-76.

23.Izzedine H, Bodaghi B, Launay-Vacher V, Deray G. Oculorenal manifestations in systemic autoimmune diseases. Am J Kidney Dis 2004;43:209-22.

24.Khairallah M, Ladjimi A, Chakroun M, Messaoud R, Ben Yahia S, Zaouali S, et al. Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 2004; 111:529-34.

25.Mochizuki M, Watanabe T, Yamaguchi K, et al. Uveitis associated with human T-cell lymphotropic virus type 1 (HTLV-1). Am J Ophthalmol 1992;114:123-9.

26.Buggage RR. Ocular manifestations of human T-cell lymphotropic virus type 1 infection. Curr Opin Ophthalmol 2003;14:420-5.

27.Khairallah M, Ben Yahia S, Ladjimi A, Zeghidi H, Ben Romdhane F, Besbes L, et al. Chorioretinal Involvement in patients with West Nile virus infection. Ophthalmology 2004;111: in press.

28.Kaiser PK, Lee MS, Martin DA. Occlusive vasculitis in a patient with concomitant West Nile virus infection. Am J Ophthalmol 2003;136:928-30.

INTRODUCTION

Retinal vasculitis, the most frequently described form of the larger group of ocular vasculitis,1,2 is a sightthreatening inflammatory eye condition that involves the retinal vessels. It may occur as an isolated idiopathic disease, as a complication of infective, or neoplastic disorders, or in association with systemic inflammatory disease (Table 1). The term retinal vasculitis is loosely used in clinical ophthalmology. However, there is not enough histological data to confirm infiltration of leukocytes within vessel wall. This is in contrast to systemic vasculitis, which is a recognised clinicopathologic process characterised by vascular inflammation and necrosis. Therefore, in this chapter we shall use the term vasculitis / vasculopathy to describe the clinical manifestation of vascular sheathing, vascular leakage, or occlusion associated with various types of intermediate and posterior uveitis.

CLINICAL FINDINGS

Retinal vasculitis may be symptomatic or asymptomatic. If the retinal vascular changes are in the periphery of the fundus without vitreous involvement, patients may have minimal or no symptoms. Patients with inflammation of the posterior retinal blood vessels and/or vitreous cells, may experience a decrease in vision or may notice floaters. Visual field scotomata

may develop and are usually related to the areas of ischaemia.

Active vascular disease is characterised by sheathing or cuffing of blood vessels, and vitreous cells. Inflammation of the macular blood vessels can cause macular oedema. Occlusive retinal vasculitis may cause cotton-wool spots representing microinfarcts, retinal oedema and intraretinal haemorrhages. Late changes secondary to vascular occlusion and remodelling include telangiectasis, microaneurysms, and ischaemia-induced neovascularisation. These clinical signs may be confirmed by fluorescein angiography, which demonstrates leakage of the dye due to breakdown of the inner blood-retinal barrier, and staining of the blood vessel wall with fluorescein. Fluorescein angiography is a more sensitive technique and will frequently show that the vasculitis is more extensive than the clinical examination suggests. In our experience, optical coherence tomography is a highly effective method in the diagnosis of macular oedema in uveitis as it provides highly reproducible measurements of retinal thickness in micrometers. In addition, it is of great value in assessing the results of treatment for uveitic cystoid macular oedema (Figure 1). The two main causes of visual loss are cystoid macular oedema and new blood vessel formation resulting from retinal ischaemia that can lead to vitreous haemorrhage and traction retinal detachment.3

Table 1: Disorders associated with retinal vasculitis

Infectious disorders

•Bacterial disorders: tuberculosis, syphilis, lyme disease, Whipple’s disease, brucellosis, Cat scratch disease, endophthalmitis.

•Viral disorders: human T cell lymphoma virus type 1, cytomegalovirus, herpes simplex virus, varicella zoster virus, Rift Valley fever virus, hepatitis, acquired immunodeficiency syndrome, West Nile virus infection.

•Parasitic disorders: toxoplasmosis.

•Rickettsial disorders: Mediterranean spotted fever.

Neurologic disorders

•Multiple sclerosis

•Microangiopathy of the brain, retina, and cochlea (Susac’s syndrome)

Malignancy

•Paraneoplastic syndromes

•Ocular lymphoma

•Acute leukaemia

Systemic Inflammatory disease

•Behçet’s disease

•Sarcoidosis

•Systemic lupus erythematosus

•Wegener’s granulomatosis

•Polyarteritis nodosa

•Churg-Strauss syndrome

•Relapsing polychondritis

•Sjögren’s A antigen

•Rheumatoid arthritis

•HLA-B27-associated uveitis

•Crohn’s disease

•Postvaccination

•Dermatomyositis

•Takayasu’s disease

•Buerger’s disease

•Polymyositis

Ocular disorders

•Frosted branch angiitis

•Idiopathic retinal vasculitis, aneurysms, and neuroretinitis

•Acute multifocal haemorrhagic retinal vasculitis

•Idiopathic recurrent branch retinal arterial occlusion

•Pars planitis

•Birdshot retinochoroidopathy

Figures 1A and B: Optical coherence tomography (OCT) of the left eye of a 26-year-old man with retinal vasculitis secondary to Behçet’s disease showing cystoid macular oedema. Macular thickness measured by the retinal thickness map was 445 micrometers. Visual acuity was 20/60 (A). Ten months after starting infliximab therapy, OCT displays normal anatomy of the macula with reduction of macular thickness to 207 micrometers. Visual acuity improved to 20/25 (B)

tuberculoprotein hypersensitivity (Eales’ disease), and human immunodeficiency virus infection (HIV). Retinal arteritis is more commonly seen in systemic lupus erythematosus, polyarteritis nodosa, and acute retinal necrosis. Intraretinal infiltrates are characteristic of infectious processes, but in the absence of these, they are pathognomonic of Behçet’s disease. Cotton wool spots are most often found in association with a systemic vasculitis. Swelling of the optic nerve head is a common nonspecific finding related to the intraocular inflammation but may also represent infiltrative disease of the nerve itself or optic nerve head vasculitis such as the case in patients with Behçet’s disease.

INFECTIOUS RETINAL VASCULITIS

TUBERCULOSIS

Retinal vasculitis affecting predominantly the veins (phlebitis) has been described in association with Behçet’s disease, tuberculosis, sarcoidosis, multiple sclerosis, pars planitis, retinal vasculitis associated with

Mycobacterium tuberculosis is an aerobic acid-fast bacillus that causes human tuberculosis. The most common manifestation of ocular tuberculosis in patients with pulmonary tuberculosis is choroiditis.4

Retinal periphlebitis with marked tendency to peripheral retinal capillary closure leading to new vessel formation was reported to be the presenting sign of tuberculosis.5,6

Ocular manifestations of tuberculosis can be due to direct infection or indirect hypersensitivity mechanisms to mycobacterial antigens when there is no defined active systemic lesion elsewhere or the lesion is thought to be inactive.5 In addition to retinal periphlebitis caused by direct infection, there is evidence to support an immune-mediated cause of retinal periphlebitis in patients with tuberculoprotein hypersensitivity (Eales’ disease). Eales’ disease

manifests as an obliterative periphlebitis (Figure 2) affecting the retina in multiple quadrants, starting at or anterior to the equator and progressing posteriorly. This inflammation induced vascular occlusion can lead to a proliferative vascular retinopathy with sequelae such as recurrent vitreous haemorrhage and traction retinal detachment (Figure 3). The disease appears most commonly to affect healthy young adults in the third and fourth decades of life. Men may be affected more often than women. The disease appears to be more prevalent in India, Pakistan, and Afghanistan.4

Although the clinical characteristic and natural course of Eales’ disease are well known, its etiopatho-

genesis is not yet well understood. Of the several aetiologies proposed, most favoured are tuberculosis and hypersensitivity to tuberculoprotein. Recently, M tuberculosis complex DNA was detected in vitreous fluid samples of Eales’ disease patients using polymerase chain reaction.7 Another study, demonstrated the presence of M. tuberculosis DNA by nested polymerase chain reaction technique in epiretinal membrane specimens from patients with Eale’s disease.8 Bacteriological examination of vitreous fluid samples did not reveal the presence of acid-fast bacilli.7 In addition, Biswas et al9 found statistically significant higher phenotype frequencies of (HLA) B5 (B51), DR1, and DR4 in patients with Eales’ disease compared with healthy people. It is postulated that individuals with the HLA predisposition may develop retinal vasculitis as a result of a cell mediated immunological tissue damage triggered by a sequestered M. tuberculosis antigen in an inactive form and clinically present as Eales’ disease.8

The management of active tuberculous retinal vasculitis or retinal vasculitis associated with tuberculoprotein hypersensitivity (Eales’ disease) requires the use of systemic steroids and appropriate antituberculous therapy to avoid reactivation of systemic illness. Rosen et al5 reported a series of patients with intraocular tuberculosis in which one of the patients with retinal vasculitis and no evidence of active systemic disease at presentation developed miliary tuberculosis following treatment with corticosteroids alone. New vessel formation associated with retinal vasculitis and capillary closure responds to panretinal photocoagulation. Early vitrectomy and adequate endolaser photocoagulation should be considered in eyes with non-resolving vitreous haemorrhage associated with active fibrovascular proliferation.10

SYPHILIS

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. The incidence of syphilis has markedly increased since the mid-1980s. Because of the protean manifestations of the disease, it has been called the “great imitator”. The ability of syphilis to mimic different ocular disorders can lead to misdiagnosis and delay in appropriate antimicrobial therapy. Syphilis, therefore, needs to be excluded in any patient with retinal vasculitis. Posterior segment

complications include vitritis, chorioretinitis, retinal vasculitis, venous and arterial occlusive disease, exudative retinal detachment, macular oedema, neuroretinitis, optic neuritis, optic atrophy, choroidal neovascular membranes, and pseudoretinitis pigmentosa. Leutic vasculitis is more commonly arterial, but an isolated periphlebitis has also been reported.11-17

TOXOPLASMOSIS

Toxoplasmosis is caused by the obligate intracellular parasite, Toxoplasma gondii. The cat is the definitive host, whereas humans are incidental hosts. Human infections may occur by either the congenital or the acquired route. The ocular lesions primarily affect the retina. The hallmark of ocular toxoplasmosis is focal necrotizing retinitis, ultimately resulting in characteristic atrophic scars. Reactivation is frequently situated adjacent to an old atrophic scar with hyperpigmentation along the borders, indicating an old infection (satellite formation). Anterior uveitis, which may be granulomatous, and a secondary rise in intraocular ocular pressure may also be noted. There may be an associated retinal vasculitis, which may be either near to or distant from the focus of active retinochoroiditis18 (Figure 4). In rare cases, the vasculitis may be occlusive, resulting in retinal infarction and consequent visual field defects. Recently, a case of frosted branch angiitis secondary to toxoplasmic retinochoroiditis was reported.19 In addition, DiazValle et al20 reported a case of acute frosted branch angiitis without necrotizing chorioretinitis associated with acquired toxoplasmosis. The patient developed late peripheral retinochoroidal scar. Similarly, Holland et al21 reported the development of intraocular inflammatory reactions including vitritis, iridocyclitis, and retinal vasculitis without necrotizing retinal lesions in individuals with acquired T. gondii infection. Foci of retinitis or inactive retinochoroidal scars were seen in the same eyes during follow-up examinations suggesting that the initial inflammation may be caused by the presence of parasite in retinal tissue. These data strongly suggest that acquired T. gondii infection should be considered in the differential diagnosis of patients with retinal vasculitis, especially in the presence of constitutional symptoms suggesting systemic toxoplasmosis. More severe or atypical ocular presentations occur in immunocompromised patients.

HUMAN T CELL LYMPHOMA VIRUS TYPE 1 (HTLV-1) ASSOCIATED UVEITIS

Human T-cell lymphotropic virus type 1 (HTLV-1), a single-stranded RNA retrovirus, is the first retrovirus to be associated with human disease. HTLV-1 is transmitted by sexual contact, by blood transfusion, from mother to child transplacentally, and via breast feeding. The infection is diagnosed by serology, demonstrating antibodies to the virus that is confirmed by Western blot analysis. HTLV-1 infection is endemic in Japan, the Caribbean islands, and parts of Central Africa and South America. The major target cell of HTLV-1 is the CD4+ T-cell. HTLV-1 infection is the established cause of adult T-cell leukaemia / lymphoma (ATL), an aggressive malignancy of CD4+ lymphocytes; HTLV-1 associated myelopathy (HAM)/ tropical spastic paraparesis (TSP), a demyelinating inflammatory disease of the spinal cord; and HTLV-1 uveitis (HU), defined as uveitis of undetermined aetiology in an HTLV-1 carrier. Clinically, HU has been described as an acute granulomatous or nongranulomatous uveal reactions that were accompanied by vitritris and retinal vasculitis. The ocular disease was considered benign, resolving over weeks in response to corticosteroid treatment, with low incidence of complications and good visual prognosis. Gray-white, granular deposits scattered on the retinal vessels in the posterior pole were noted. Similar material was also found to deposit on the vitreoretinal interface of the foveolar areas. In addition, retinal vasculitis with

sheathing of retinal veins in the periphery was described in patients with HTLV-1-associated myelo- pathy.22-24 Recently, Nakao and Ohba25 reported three HTLV-1-positive Japanese teenagers presenting with extensive retinal periphlebitis resembling frosted branch angiitis. The retinal vascular disease responded poorly to systemic corticosteroids, had a smoldering course, and eventually resulted in diffuse chorioretinal degeneration. Levy-Clarke et al26 reported a patient with ATL presenting as a bilateral retinal vasculitis associated with necrotizing retinitis. These cases suggest that HTLV-1 should be included in the differential diagnosis of retinal vasculitis, particularly in patients from endemic areas.

CYTOMEGALOVIRUS

In the majority of cases, cytomegalovirus (CMV) retinitis is a manifestation of AIDS, with CMV retinitis being the most common ocular infection in these patients. The classic description of CMV retinitis is one of scattered yellow-white areas of necrotizing retinitis with variable degrees of haemorrhage and mild vitreous inflammation (“cottage cheese with catsup” or “pizza pie” retinopathy). The pathway of expanding lesions can be predicted by the appearance of venous sheathing or white dots distal to the leading edge. CMV retinitis is often accompanied by varying amounts of retinal vasculitis consisting primarily of perivenous sheathing.27,28 Frosted branch angiitis was described in patients with AIDS associated with small patches of

CMV retinitis.29,30 Perivasculitis of the peripheral vessels involving veins more often than arteries was described in patients with AIDS. CMV retinitis was not seen in these patients. The vasculitis was thought to be a noninfectious retinopathy associated with AIDS.31,32 Recently, Fine et al33 reported a case of HIV-infected child with frosted branch angiitis without CMV retinitis that was refractory to specific anti-cytomegalovirus therapy. The angiitis only improved after subsequent treatment with systemic corticosteroids suggesting that the frosted branch angiitis in this patient was not attributed to cytomegalovirus.

ACUTE RETINAL NECROSIS

Acute retinal necrosis is caused by viruses of the herpes group, mainly varicella zoster, herpes simplex types 1 and 2, and rarely, cytomegalovirus.34-35 The prominent features of acute retinal necrosis include peripheral necrotizing retinitis, retinal arteritis, and a prominent inflammatory reaction in the vitreous and anterior chamber (Figure 5). Optic neuritis occurs in many affected eyes, and complicated rhegmatogenous retinal detachments often are encountered as a late sequela of the condition.36 The disease can progress rapidly with vision loss due to macular involvement, retinal detachment, or optic neuropathy. Vasculitis is predominantly affecting peripheral arteries with closure probably at the origin of the peripheral necrosis and is suspected to be due to antigen-antibody complexes.

RIFT VALLEY FEVER VIRUS

Rift valley fever is an arthropod-borne phlebovirus disease caused by Bunyaviridae, an RNA virus with a diameter of 94 to 100 nm that is transmitted to humans through a bite by infected mosquitoes or through direct contact with infected animals. Rift Valley fever virus can cause retinitis, occlusive retinal vasculitis, cotton-wool spots, retinal haemorrhages, and retinal oedema37,38 (Figure 6).

WEST NILE VIRUS INFECTION

West Nile virus (WNV) is a single-stranded RNA flavivirus endemic to Africa, Asia, Australia, and Europe. It was first detected in the United States in 1999 during a meningoencephalitis epidemic in New York City. It belongs to the Japanese encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, and Kunjin virus. Birds are the natural hosts for the virus, and the virus can be transmitted from them to human and other animals by the bite of an infected mosquito. The incubation period of the WNV ranges from 3 to 14 days. Approximately 20% of infected humans become symptomatic with fever, and typically only half of them are ill enough to seek medical attention. More severe symptoms include fever, malaise, anorexia, nausea, vomiting, eye pain, headache, myalgia, arthralgia, rash, and lymphadenopathy. The infection can progress to a meningoencephalitis with symptoms of headache, stiff neck, weakness, and confusion. Advanced age, immunosuppression and