Ocular Vasculitis: A Multidisciplinary Approach
Carl P. Herbort; Luca Cimino; Ahmed M. Abu El Asrar
Curr Opin Rheumatol 17(1):25-33, 2005. Â© 2005 Lippincott Williams & Wilkins
Abstract and Introduction
Purpose of Review: The ophthalmologist has direct visual access to inflamed vessels when examining the retina, and vasculitis in ophthalmology has so far mainly referred to retinal vasculitis. In the past few years the means to explore vasculitis in the ocular sphere have improved. Indocyanine green angiography now enables the analysis of choroidal inflammatory vasculopathy as well as vasculitis of the sclera (scleritis) and episclera (episcleritis) in addition to retinal vasculitis. Because vasculitis detected by the ophthalmologist can be the presenting sign of a systemic disease and has to be approached in a multidisciplinary fashion, the emerging term ocular vasculitis, instead of retinal vasculitis, should be used in the future. The term covers vasculitis affecting all structures of the eye and the periocular tissues as detailed in this article. The ocular findings have to be integrated within the established and accepted classification of systemic vasculitis, which is divided into primary vasculitides, where the vessel itself is the target of the inflammatory reaction, and secondary vasculitides, caused by other inflammatory processes. This review will deal with recently published articles on ocular vasculitis, including its clinical aspects, its link with systemic diseases, and its investigation and management. The discussion will be conducted within the framework of the new classification put forward here.
Recent Findings: Novel imaging techniques such as indocyanine green angiography have made it possible to explore inflammation of choroidal vessels and of scleral vasculitis in addition to retinal vasculitis, contributing to the global concept of ocular vasculitis. It has been shown, in particular, that the choriocapillaris, a vascular structure adjacent to the retina, can be the site of a primary inflammatory vasculopathy unrecognized so far. Most of the recent articles cited, however, deal not so much with new findings but with the integration of ocular pathologic changes into the systemic diseases they are part of. New knowledge about disease mechanisms and novel therapeutic modalities with biologic agents cited in this review are coming from other fields but have contributed to progress in the management of ocular vasculitis.
Summary: New investigational techniques of vasculitis in ocular structures other than the retina have contributed to the development of the global concept of ocular vasculitis. This review shows the importance of promoting a comprehensive and global classification of ocular vasculitis compatible with the concepts accepted for systemic vasculitis to contribute to its multidisciplinary approach.
In the ophthalmic literature, the term vasculitis classically refers to retinal vasculitis, and most of the published work on vasculitis in the ocular field concerns retinal vasculitis. Classically, retinal vasculitis was divided into entities localized to the retina and into systemic diseases involving the eye. Vasculitis in the ocular sphere is, however, not limited to the retina, but can also touch the choroid, the sclera, the periocular tissue, and the ocular adnexa. Therefore, the more global concept of ocular vasculitis including retinal vasculitis should now be put forward as an emerging terminology because it is clinically more relevant for the appraisal of vasculitis in a multidisciplinary approach. Such a terminology is emerging presently because we now have the means to explore efficiently not only retinal vasculitis as was the case so far with fluorescein angiography but other vasculitic ocular involvement. Thanks to indocyanine green angiography (ICGA), we are now also able to explore choroidal inflammatory vasculopathy that was previously inaccessible. ICGA also makes it possible to analyze more precisely the vasculitic process in anterior scleritis.
At the level of the choroid, this new technology has fundamentally changed our appraisal of intraocular inflammation and vasculitis because it allows us to have imaging access to the inflamed choroidal vessels. The technique allows differentiation between at least two choroidal inflammatory vasculopathies, the first involving the choriocapillary circulation at the origin of a group of diseases classified within the new concept of primary inflammatory choriocapillaropathies, and the second involving larger choroidal vessels defined as stromal choroidal inflammatory vasculopathies.[3,4]
Because the ophthalmologist can detect retinal or choroidal vasculitis or other lesions caused by a vasculitic process such as episcleritis, scleritis, and orbital disease that may all be part of a systemic disease, it is important to classify and integrate ocular vasculitis within the accepted classification of systemic vasculitis.
In 1992, the Chapel Hill consensus conference on the nomenclature of systemic vasculitis generated a uniformly accepted classification of primary systemic vasculitides based on histopathologic changes showing that the vessel wall is the primary target. These entities were differentiated from secondary vasculitides in which vessel inflammation may be prominent but is a phenomenon secondary to other inflammatory processes. Primary systemic vasculitides were subdivided according to the size of the vessel principally involved into large, medium, and small vessel vasculitis.
The emerging term ocular vasculitis should encompass episcleritis, scleritis including peripheral ulcerative keratitis, retinal vasculitis, choroidal vasculitis, optic nerve vasculitis, and papillitis and should be extended to the orbit and adnexa because all these locations can produce vasculitis-induced ophthalmologic signs diagnosed by the ophthalmologist.
Such a global approach to the vasculitic process in the ocular field will surely be clinically more relevant to initiate a comprehensive multidisciplinary approach when this is necessary.
Ocular vasculitis following the accepted classification of systemic vasculitis should likewise be divided into lesions caused by primary systemic vasculitides and lesions caused by secondary systemic vasculitides. In addition to systemic vasculitides that involve the eye, there are entities wherein the vasculitic process is or seems to be limited to the eye. The mechanism is suspected to be primary in some of these entities, and they can provisionally be classified into primary inflammatory vasculopathies limited to the eye, such as the primary choriocapillaropathies recently individualized. However, the primary nature of the vascular insult has not yet been proved, as we do not have any histology, and therefore these diseases should be called inflammatory vasculopathies rather than vasculitides. In most of these local entities the inflammation of ocular vessels is, however, secondary to another inflammatory mechanism, such as in birdshot chorioretinopathy, wherein the primary immune-mediated mechanism is a granulomatous inflammatory reaction. Infections represent the other factors causing secondary inflammatory vasculopathy that may be limited to the eye, such as acute retinal necrosis caused by the ubiquitous herpesviruses but that occurs only in the eye.
Following this principle, we have come up with a detailed classification of ocular vasculitis that takes into account four main subclasses: (1) primary vasculitis or inflammatory vasculopathy limited to the eye, a group recently individualized with no histopathologic information yet; (2) systemic primary vasculitis involving the eye; (3) secondary vasculitis or inflammatory vasculopathy limited to the eye; and (4) the vast group of systemic secondary vasculitic entities involving the eye, whether immune-mediated, infectious, drug-induced. or neoplastic (Table 1). The entities from these four subclasses have been listed under the different ocular structures from front to back when they cause lesions in these structures (Table 1). Although this classification is as complete as possible, it is by far not exhaustive. As for ocular involvement of primary systemic vasculitides, the authors followed the classification described by Jennette and Falk based on the Chapel Hill consensus conference on the nomenclature of systemic vasculitis and the ocular counterpart article that discussed the ocular manifestations of these primary systemic vasculitides.[6**]
With this classification as a background, we reviewed the recent literature contributing to better knowledge of ocular vasculitis regarding its appraisal and management. The selection of articles is the result of the authors' choice, is probably biased, and does not aim to be fully exhaustive but was nevertheless meant to be as complete as possible, taking into consideration the limited space provided for this review.
Investigational and Diagnostic Methods of Ocular Vasculitis and Disease Mechanisms
Significant progress in the investigation of ocular vasculitis is represented by the introduction of ICGA, which has been routinely, although not yet universally, used for the past few years. In the ocular fundus, this technique uses the unique properties of the indocyanine green molecule, which, after being injected intravenously, causes an infrared fluorescence in the choroid that can be seen through the retinal pigment epithelium. Until ICGA was introduced, the choroidal vessels could not be analyzed because the choroidal fluorescence caused by the fluorescein molecule used for fluorescein angiography was blocked by the retinal pigment epithelium. Therefore, little was known about the inflammatory behavior of choroidal vessels. The technique showed that two main patterns of choroidal inflammatory vasculopathy occur at the level of the choroid, namely, inflammation of the choriocapillaris and inflammation of the larger stromal vessels.
The protein-bound indocyanine green is a large molecule that impregnates tissues when it is extruding from inflamed vessels. This property also makes the method useful in evaluating the vasculitic process in episcleritis and scleritis, where it shows the extension of the inflamed vessels and seems to be useful for distinguishing between episcleritis, a more benign process, and scleritis, a more severe condition, especially in case of arteriolar closure. Several publications on disease mechanisms deserve to be cited. A Dutch group found pathologic endothelial cell activation and a hypercoagulability state in ocular BehÃ§et disease, possibly explaining occlusive disease in some patients, although the authors could not establish a correlation between disease pattern and hypercoagulability.[8*] The association of severe vaso-oclusive retinopathy in systematic lupus erythematosus with the presence of antiphospholipid antibodies was shown in a literature review that stressed the place of anticoagulation in addition to immunosuppression in these cases.
Primary Vasculitis or Inflammatory Vasculopathy Limited to the Eye
The availability of ICGA made it possible to have new insights into choroidal inflammation. It allowed better classification of choroiditis and a better understanding of disease mechanisms. Diseases such as acute posterior multifocal placoid pigment epitheliopathy, multiple evanescent white dot syndrome, multifocal choroiditis, and serpiginous choroiditis, thought to be diseases of the retinal pigment epithelium, were shown to be due to inflammation of the choriocapillaris, and all these diseases could be regrouped under the term inflammatory choriocapillaropathies. It is still unknown whether the mechanism is a primary inflammation of the choriocapillaris or whether choriocapillaris involvement is secondary. Furthermore, no histopathologic description of these diseases is available. ICGA has further identified the inflammatory eye diseases that cause inflammation to the choroidal stromal vessels in addition to retinal vasculitis. The new classification of choroiditis and choroidal inflammatory vasculopathies based on ICGA has been discussed in a recently published book on uveitis.[10*-12*]
Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVIN) constitute a rare bilateral condition including retinal arteritis, aneurysmal dilatations of the retinal and optic nerve head arterioles, neuroretinitis, and uveitis that is limited to the eye. The association of this condition with allergic fungal sinusitis, recently reported, seems to indicate that a systemic hypersensitivity mechanism could be at the origin of idiopathic retinal vasculitis, aneurysms, and neuroretinitis, which would imply that the vasculitis is possibly secondary.
Primary Systemic Vasculitides Involving the Eye and Adnexa
Recent publications in this field are mostly case reports or review articles on the involvement of the eye and adnexa in primary systemic vasculitides. A crucial article is the extensive review of the ocular lesions in primary systemic vasculitides that follows the Chapel Hill consensus conference classification.[6**]
The authors realized the importance of integrating ocular vasculitis into this well-established classification. For each of the large, medium, and small vessel vasculitides, ocular manifestations have been compiled.[6**] McDonald et al. describe a case of Takayasu arteritis in a child with bilateral uveitis and cystoid macular edema, an unusual ocular involvement, which responded well to the administration of corticosteroids and was not due to ocular ischemia. In their series of nine patients with Wegener granulomatosis, Biswas et al. showed that scleritis with peripheral corneal ulceration was the most frequent ocular sign, in contrast to the predominant orbital involvement usually reported in the literature. Two case reports of ocular involvement in Churg-Strauss syndrome stress the two main types of ocular lesions: orbital involvement in the form of pseudotumors, presenting also rarely as a myositis that is usually antineutrophil cytoplasmic antibody (ANCA) negative, and the ischemic-vasculitic type, usually ANCA positive, with serious consequences on the retina and visual function.[16,17]
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 (nearly 100%) association with the HLA-A29 major histocompatibility antigen. Recently the first autopsy case showed that the choroidal inflammation is characterized by granulomatous foci and choroidal vasculitis, indicating that the vasculopathy in birdshot chorioretinopathy is secondary to a granulomatous inflammation.
An angiographic study using fluorescein and ICGA showed that retinal vasculitis and choroidal inflammation occur and develop independently from each other.[19*] Choroidal disease responds well to corticosteroid and immunosuppressive therapy, whereas retinal involvement is more resistant to therapy and is responsible for the severe functional impairment that occurs in some cases.[19*] Eale disease, often also called tuberculoprotein hypersensitivity vasculitis because of a hyperpositive tuberculin skin test present in these patients, includes peripheral retinal periphlebitis, nonperfusion, and recurrent vitreous hemorrhages caused by neovascularization. A recent study showed that reactive nitrogen species and reactive oxygen species were elevated in Eale patients, indicating that free radicals are involved in mediating tissue damage.[2 Sympathetic ophthalmia is a bilateral granulomatous inflammation thought to be caused by sensitization 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 is confirmed in future, that the inflammation can have a systemic expression in some cases.
Secondary Systemic Vasculitides Involving the Eye and Adnexa
Susac syndrome is a microangiopathy involving the arterioles of the brain, the retina, and the cochlea and clinically presents with subacute encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Primary vessel inflammation has not been proved and we have classified the disease in the secondary systemic vasculitides until another classification is demonstrated. A recent series of four patients with Susac syndrome, preceded by an editorial by Susac, gives a complete review of this underdiagnosed disease, with good MRI images and histopathology of arteriolar lesions.
A multitude of ocular sites can be involved by the vasculitis associated with inflammatory bowel diseases. Episcleritis and scleritis are associated with inflammatory bowel diseases in as many as 29% and 18% of patients, respectively. Uveitis is usually nongranulomatous and is mostly associated with the presence of the HLA-B27 major histocompatibility antigen. Peripheral ulcerative keratitis can be present alone but can also be seen with scleritis. Orbital pseudotumor and optic neuropathy have also been described, as has retinal vasculitis. Ocular involvement in association with inflammatory bowel diseases has been reviewed exhaustively in a recent review. Similar review work has been done to identify the lesions shared by the kidney and the eye in primary and secondary vasculitic processes.[25*] Numerous 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 recognized pathologic changes. Rickettsial diseases are known to cause retinal vasculitis. A recent series of 30 patients with Mediterranean spotted fever caused by Rickettsia conorii showed that approximately half of the patients had signs of retinal vasculitis on clinical examination or by fluorescein angiography, and this cause should be considered in endemic areas.[26*]
Human T cell lymphotropic virus type 1 (HTLV-1), a RNA retrovirus endemic in Japan, the Caribbean islands, and parts of central Africa and South America, causes adult T cell lymphoma, HTLV-1 associated myelopathy, and tropical spastic paresis. Associated ocular inflammation, first described by Mochizuki et al. in 1992, includes granulomatous and nongranulomatous anterior uveitis, intermediate uveitis, retinochoroidal lesions, and retinal vasculitis. Buggage[28*] recently published a very complete review article on the ocular involvement and ocular vasculitis in HTLV-1 infection.
The West Nile virus is one of the emerging infectious agents that cause 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, 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. Approximately 20% of infected persons are symptomatic and experience a flu-like illness, which develops 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 Âµm to 1500 Âµm and a linear disposition. Associated retinal vascular changes include intraretinal hemorrhages, white-centered hemorrhages, focal vascular sheathing, and retinal vascular leakage. Thanks to the work of a Tunisian group that has published the largest series so far on ocular involvement due to West Nile virus infection and that performed a prospective study during the last outbreak in their country, the clinical picture has been well established.[29**] Occlusive retinal vasculitis has been described in association with West Nile virus infection.[3
Progress in the Management of Vasculitis Involving the Eye
Corticosteroid therapy of ocular inflammatory diseases and vasculitis has recently been rejuvenated because of new therapeutic modalities that allow the delivery of high-dose corticosteroids to the inside of the eye by the use of implanted slow-release devices or direct intraocular injections. Especially conditions localized to the eye or with predominant ocular involvement or with unilateral ocular disease will profit most from these potent local treatments, with consecutive reduction of systemic therapy. Ciulla et al.[31*] gave a detailed review of these new intraocular corticosteroid delivery techniques and reviewed present-day indications for corticosteroid use in ocular posterior segment disease, including inflammatory diseases and vasculitis. Several articles deal with the new therapeutic modalities applied to uveitis and vasculitis. A German group published an extensive review that included their own work on the use of interferon-a in BehÃ§et vasculitis. They showed that interferon-a is effective in the treatment of ocular BehÃ§et disease, including posterior uveitis and vasculitis resistant to other treatments, and achieved preservation of visual function.[32*] Infliximab, a tumor necrosis factor-a inhibitor, is increasingly used in the treatment of uveitis and ocular vasculitis. Murphy et al. treated a heterogenous group patients with inflammatory conditions, of whom six of seven patients had ocular vasculitic disease, including two cases of retinal vasculitis and four cases of scleritis. In the six patients in whom treatment could be continued, infliximab showed a positive effect, inducing remission in five patients and allowing significant reduction of immunosuppression in all six. One group reported success in the treatment of ocular inflammation in BehÃ§et disease. Thereafter, a larger Japanese series showed the effectiveness of infliximab in the treatment of ocular involvement in BehÃ§et disease.[35*] Infliximab significantly reduced the mean numbers of ocular attacks compared with the pre-infliximab observation period, both in the group treated with 5 mg/kg and in the group treated with 10 mg/kg. The management of tuberculoprotein hypersensitivity vasculitis, sometimes called Eale disease, has not been well established and is often unsuccessful. El-Asrar and Al-Kharashi published a series of 19 patients who were treated aggressively with systemic steroids, antituberculous therapy, full panretinal photocoagulation, and early vitrectomy if necessary.
Vasculitic involvement of the eye should no longer be reduced to retinal vasculitis alone. The emerging term ocular vasculitis should apply to all ocular and periocular lesions caused by a vasculitic process, including episcleritis, scleritis, peripheral ulcerative keratitis, retinal vasculitis, choroidal vasculitis, and 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 to the great proportion of cases of ocular vasculitis that are part of a systemic disease.
Table 1. Classification of Ocular Inflammatory Vasculopathy or Vasculitis
Papers of particular interest, published within the annual period of review, have been highlighted as:
* Of special interest
** Of outstanding interest
Herbort CP, Guex-Crosier Y, LeHoang P: Schematic interpretation of indocyanine green angiography. Ophthalmology 1994, 2:169-176.
Herbort CP, Bodaghi B, LeHoang P: Angiographie au vert d'indocyanine au cours des maladies inflammatoires: principes, interpretation schÃ©matique, sÃ©miologie et intÃ©rÃªt clinique. J Fr Ophthalmol 2001, 24:423-447.
Cimino L, Auer C, Herbort CP: Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies. Ocul Immunol Inflamm 2000, 8:275-283.
Bouchenaki N, Cimino L, Auer C, et al.: Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography. Klin Monatsbl Augenheilkd 2002, 219:243-249.
Jennette JC, Falk RJ: Small-vessel vasculitis. N Engl J Med 1997, 337:1512-1523.
Perez VL, Chavala SH, Ahmed M, et al.: Ocular manifestations and concepts of systemic vasculitides. Surv Ophthalmol 2004, 49:399-418.
** The authors review the ocular lesions found in primary systemic vasculitides. This is a landmark article that represents a step forward in the concept of ocular vasculitis and that promotes the classification of ocular vasculitis following the system universally accepted for systemic vasculitides.
Guex-Crosier Y, Durig J: Anterior segment indocyanine green angiography in anterior scleritis and episcleritis. Ophthalmology 2003, 110:1756-1763.
Probst K, Fijnheer R, Rothova A: Endothelial cell activation and hypercoagulability in ocular BehÃ§et's disease. Am J Ophthalmol 2004, 137:850-857.
Au A, O'Day J: Review of severe vaso-occlusive retinopathy in systemic lupus erythematosus and the antiphospholipid syndrome: associations, visual outcome, complications and treatment. Clin Exp Ophthalmol 2004, 32:87-100.
Herbort CP: Choroiditis, general considerations and classification. In: Essentials in Ophthalmology: Uveitis and Immunological Disorders. Edited by Pleyer U, Mondino B. Berlin, Heidelberg, New York: Springer; 2004:202-208.
* A new classification of choroiditis and choroidal inflammatory vasculopathy is given, based on ICGA and not on clinical appearance as had been the case so far.
Cimino L, Mantovani A, Herbort CP: Primary inflammatory choriocapillaropathies. In: Essentials in Ophthalmology: Uveitis and Immunological Disorders. Edited by Pleyer U, Mondino B. Berlin, Heidelberg, New York: Springer; 2004:209-231.
* The primary inflammatory choriocapillaropathies result from inflammation of the choriocapillaris. Disease characteristics and physiopathology of the entities newly assembled in this group are discussed.
Bouchenaki N, Herbort CP: Stromal choroiditis. In: Essentials in Ophthalmology: Uveitis and Immunological Disorders. Edited by Pleyer U, Mondino B. Berlin, Heidelberg, New York: Springer; 2004:234-253.
* Primary inflammation of the choroidal stroma characterizes the diseases regrouped under the term stromal choroiditis. These are mostly granulomatous diseases that cause secondary stromal inflammatory vasculopathy.
Abu El-Asrar AM, Jestaneiah S, Al-Serhani AM: Regression of aneurysmal dilatations in a case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) associated with allergic fungal sinusitis. Eye 2004, 18:197-201.
McDonald MA, Ojaimi E, Favilla I: Anterior uveitis in a child with Takayasu's arteritis. Clin Experiment Ophthalmol 2004, 32:336-339.
Biswas J, Babu K, Gopal L, et al.: Ocular manifestations of Wegener's granulomatosis. Indian J Ophthalmol 2003, 51:217-223.
Billing K, Malhotra R, Selva D, et al.: Orbital myositis in Churg-Strauss syndrome. Arch Ophthalmol 2004, 122:393-396.
Partal A, Moshfeghi DM, Alcorn D: Churg-Strauss syndrome in a child: retina and optic nerve findings. Br J Ophthalmol 2004, 88:971-972.
Gaudio PA, Kaye DB, Brooks Crawford J: Histopathology of birdshot retinochoroidopathy. Br J Ophthalmol 2002, 86:1439-1441.
Herbort CP, Probst K, Cimino L, et al.: Differential inflammatory involvement in retina and choroids in birdshot chorioretinopathy. Klin Monatsbl Augenheilkd 2004, 221:351-356.
* On the basis of ICGA findings, the authors show that birdshot chorioretinopathy is an inflammatory disease limited to the eye that shows primary stromal disease associated with primary retinal disease, indicating that the inflammatory targets are both the retina and the choroidal stroma.
Rajesh M, Sulochana KN, Punitham R, et al.: Involvement of oxidative and nitrosactive stress in promoting retinal vasculitis in patients with Eale's disease. Clin Biochem 2003, 36:377-385.
KadayifÃ§ilar S, IrkeÃ§ M, Eldem B: Sympathetic ophthalmia associated with ocular and cerebral vasculitis: an angiographic and radiologic study. Eur J Ophthalmol 2003, 13:584-587.
Susac J: Susac's syndrome. AJNR Am J Neuroradiol 2004, 25:351-352.
Do TH, Fisch C, Evoy F: Susac syndrome: report of 4 cases and review of the literature. AJNR Am J Neuroradiol 2004, 25:382-388.
Ghanchi FD, Rembacken BJ: Inflammatory bowel disease and the eye. Surv Ophthalmol 2003, 48:663-676.
Izzedine H, Bodaghi B, Launay-Vacher V, et al.: Oculorenal manifestations in systemic autoimmune diseases. Am J Kidney Dis 2004, 43:209-222.
* This is a detailed review of the ocular and renal pathologic changes caused by immune-mediated diseases, including primary and secondary systemic vasculitides.
Khairallah M, Ladjimi A, Chakroun M, et al.: Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 2004, 111:529-534.
* This is one of the largest series describing ocular involvement, including vasculitis, in rickettsial infections
Mochizuki M, Watanabe T, Yamaguchi K, et al.: Uveitis associated with human T-cell lymphotropic virus type 1 (HTLV-1). Am J Ophthalmol 1992, 114:123-129.
Buggage RR: Ocular manifestations of human T-cell lymphotropic virus type 1 infection. Curr Opin Ophthalmol 2003, 14:420-425.
Khairallah M, Ben Yahia S, Ladjimi A, et al.: Chorioretinal involvement in patients with West Nile virus infection. Ophthalmology 2004, 111:in press.
** So far, this is the only large series and prospective study on ocular lesions associated with West Nile virus infection.
Kaiser PK, Lee MS, Martin DA: Occlusive vasculitis in a patient with concomitant West Nile virus infection. Am J Ophthalmol 2003, 136:928-930.
Ciulla TA, Walker JD, Fong DS, et al.: Corticosteroids in posterior segment disease: an update on new delivery systems and new indications. Curr Opin Ophthalmol 2004, 15:211-220.
* This is an essential review of new ocular delivery methods for corticosteroids that will determine new therapeutic attitudes in the management of intraocular inflammation.
KÃ¶tter I, GÃ¼naydin I, Zierhut M, et al.: The use of interferon alpha in BehÃ§et disease: review of the literature. Semin Arthritis Rheum 2004, 33:320-335.
Murphy CC, Ayliffe WH, Booth A, et al.: Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 2004, 111:352-356.
Sfikakis PP, Theodossiadis PG, Katsiari CG, et al.: Effect of infliximab on sight-threatening panuveitis in BehÃ§et's disease. Lancet 2001, 358:295-296.
Ohno S, Nakamura S: Hori S, et al.: Efficacy, safety and pharmacokinetics of multiple administration of infliximab in BehÃ§et's disease with refractory uveoretinitis. J Rheumatol 2004, 31:1362-1368.
* This report of a multicenter trial details the results of the use of infliximab for ocular involvement in BehÃ§et disease.
Abu El-Asrar A, Al-Kharashi SA: Full panretinal photocoagulation and early vitrectomy improve prognosis of retinal vasculitis associated with tuberculoprotein hypersensitivity (Eale's disease). Br J Ophthalmol 2002, 86:1248-1251.
Correspondence to Carl P. Herbort, Inflammatory Eye Diseases, La Source Eye Centre 2, Avenue des BergiÃ©res CH-1004, Lausanne, Switzerland. Tel: + 41 21 643 15 15; fax: + 41 21 648 60 10; e-mail: email@example.com
ICGA = indocyanine green angiography;
Carl P. Herborta, Luca Ciminob and Ahmed M. Abu El Asrarc
aInflammatory Eye Diseases, La Source Eye Centre, and University of Lausanne, Lausanne, Switzerland; bOcular Immunology Unit, Archispedale Santa Maria, Nuova Reggio Emilia, Italy; and cDepartment of Ophthalmology, King Abdulaziz University Hospital Riyadh, Saudi Arabia
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