IGG4-RELATED OPHTHALMIC DISEASE PRESENTING AS CHOROIDAL AND ORBITAL LESIONS.

PURPOSE: To report a case of IgG4-related ophthalmic disease (IgG4-ROD) which presented as choroidal and orbital lesions. METHODS: Case report. RESULTS: A 64-year-old man presented with left eye photopsias and a history of IgG4-related perirenal fibrosis. Fundoscopic examination showed multiple bilateral yellow choroidal lesions, and optical coherence tomography showed multiple choroidal lesions. Magnetic resonance imaging of the orbits showed an enhancing lesion present circumferential to the optic nerve, but greater medially, abutting the posterior surface of the left globe. Workup for infectious, autoimmune, and malignant etiologies was negative, and the patient has responded well to treatment with rituximab. CONCLUSION: IgG4-related disease is a systemic fibroinflammatory disease, which often presents in another location, as in our patient. In cases of uncertain choroidal and orbital lesions, a thorough workup for other etiologies is indicated, and lymphoma must be ruled out. Steroids are the mainstay of treatment for IgG4-ROD, however, small case series and our patient responded well to rituximab. To our knowledge, this is the first reported case of choroidal and orbital lesions secondary to IgG4-ROD.

Disseminated tuberculosis presenting as hemophagocytic lymphohistiocytosis in an immunocompetent adult patient: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a frequently fatal and likely underdiagnosed disease. It is a rare occurrence in adults and usually secondary to an insult such as viral infections, bacterial infections, autoimmune connective tissue disorders, malignancies and immunocompromised states, in contrast to its childhood counterpart, which is due to a genetic defect but may share some of same genetic etiologies. It is characterized by multisystem inflammation due to unregulated proliferation and infiltration of macrophages and CD8 T cells in the bone marrow, which leads to phagocytosis of red blood cells, platelets, lymphocytes and their precursors. CASE PRESENTATION: A 40-year-old Sri Lankan woman presented with a high-grade fever of 2 weeks' duration and the initial workup, including a thorough clinical examination, and all the investigations, including a septic screen, were normal. On the 18th day of hospital admission, she was found to have yellowish retinal lesions, which were confirmed as choroid tubercles by the consultant eye surgeon. Two days later she became pancytopenic and a bone marrow biopsy confirmed the diagnosis of hemophagocytic lymphohistiocytosis. She was treated with conventional category-1 antituberculous drugs and an initial 2 weeks with high-dose oral dexamethasone. All the choroid tubercles gradually disappeared and she recovered completely without any complications. CONCLUSIONS: In an adult patient with hemophagocytic lymphohistiocytosis, it is pivotal to understand the underlying etiology, as it needs extensive immunosuppression. If this patient had been treated with immunosuppressants without antituberculous medications, it would have been lethal with disseminated or central nervous system tuberculosis. So, in areas where tuberculosis is endemic, if no underlying cause is found, it may be worth considering antituberculous treatment for these patients. Re-evaluation with thorough clinical examination is of utmost importance in any patient with pyrexia of unknown origin as well as in any disease with unusual manifestations.

Birdshot retinochoroidopathy review.

Birdshot retinochoroidopathy (BSRC) is a distinct type of posterior uveitis originally described in the 1940s. Its characteristics include minimal anterior segment inflammation and diffuse posterior choroidopathy with vitritis and retinal vasculitis. The precise etiology of this disease is yet to be elucidated. However, various treatment modalities have been employed with the ultimate goal of durable remission of this vision threatening intraocular disease. The purpose of this review is not only to emphasize the importance of recognizing BSRC, but also to discuss the new discoveries, immune mediators, current and new therapies, and techniques applied to monitor and accomplish disease remission.

Birdshot retinochoroidopathy review / Revisão sobre retinocoroidopatia do tipo "birdshot"

Birdshot retinochoroidopathy (BSRC) is a distinct type of posterior uveitis originally described in the 1940s. Its characteristics include minimal anterior segment inflammation and diffuse posterior choroidopathy with vitritis and retinal vasculitis. The precise etiology of this disease is yet to be elucidated. However, various treatment modalities have been employed with the ultimate goal of durable remission of this vision threatening intraocular disease. The purpose of this review is not only to emphasize the importance of recognizing BSRC, but also to discuss the new discoveries, immune mediators, current and new therapies, and techniques applied to monitor and accomplish disease remission.

Retinocoroidopatia do tipo "birdshot" é um tipo de uveíte posterior originalmente descrita na década de 1940. Achados característicos incluem inflamação mínima do segmento anterior, retinocoroidopatia difusa associada à vitreíte e vasculite retiniana. A etiologia da doença ainda não foi completamente definida, entretanto várias modalidades de tratamento têm sido utilizadas com o objetivo de atingir a remissão. O objetivo desta revisão é enfatizar não só a importância do reconhecimento da doença como também discutir novas descobertas relacionadas a mediadores imunes, formas de tratamentos e como monitorar a doença.

Congenital toxoplasmosis in southeastern Brazil: results of early ophthalmologic examination of a large cohort of neonates.

OBJECTIVE: To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening. DESIGN: Cross-sectional analysis of a cohort. PARTICIPANTS: A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil. METHODS: From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed. MAIN OUTCOME MEASURES: Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded. RESULTS: Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%). CONCLUSIONS: A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement ( approximately 80%) and many active lesions (in approximately 50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.

Ocular lesions in Watanabe heritable hyperlipidemic rabbits.

Hyperlipidemic ocular lesions are described for Watanabe heritable hyperlipidemic (WHHL) rabbits. Male WHHL rabbits 8 months old exhibited serum hyperlipidemia and ophthalmoscopically yellowish-white lesions along the corneoscleral junction and in the iris. Histopathologically, foamy macrophages aggregated in the stroma of the cornea, iris, and ciliary body were observed. These findings have been interpreted as lipid keratopathy. In addition, multiple clusters of a large number of foamy macrophages occurred throughout the choroid and sclera in association with the blood vessels. The lesions in the choroid and sclera could not be detected ophthalmoscopy, yet were much more prominent than those in the cornea, iris, and ciliary body, suggesting greater involvement and earlier onset of lipidosis at these sites associated with hyperlipidemia in WHHL rabbits.

Photodynamic therapy for inflammatory choroidal neovascularisation unresponsive to immunosuppression.

AIM: To report on visual and angiographic outcomes of a consecutive series of patients with inflammatory choroidal neovascular membranes (CNV) unresponsive to systemic immunosuppression treated with photodynamic therapy (PDT). METHODS: The medical records of six consecutive patients with inflammatory CNVs that failed to respond to systemic immunosuppression and that later underwent PDT were retrospectively reviewed. Patient demographics, visual acuity, and fluorescein angiographic findings were evaluated. RESULTS: There were five females and one male with a mean age of 40.8 years (range 35-58 years). Four patients had clinical features consistent with punctate inner choroidopathy and two with presumed ocular histoplasmosis. In all cases clinical signs of CNV activity, including subretinal fluid, subretinal blood, hard exudates, and/or recent decrease in visual acuity were present prior to PDT. All patients had been treated with high dose systemic immunosuppressants, which failed to induce regression of the CNV and/or to improve vision. The CNVs were subfoveal in five patients and juxtafoveal in one; all were classified as predominantly classic. Following PDT an improvement in vision occurred in all cases (median improvement of 18 letters, range 3-42 letters). At last follow up, signs of decreased activity in the CNV were detected in all cases. Patients were followed for a median of 10 months (range 9-20 months). CONCLUSION: PDT appears to be a useful option in the management of patients with inflammatory CNVs unresponsive to immunosuppressive therapies.

Right active retinitis and left focal retinochoroidal scar in a girl with congenital toxoplasmosis.

In congenital cases, ocular toxoplasmosis often presents as a focal whitish fluffy lesion in the retina adjacent to an inactive chorioretinal scar. We examined a girl who has visible floaters in the right eye. The patient had focal active retinitis in the right fundus, a focal chorioretinal scar in the left fundus, a positive enzyme-linked immunosorbent assay (ELISA) for IgG anti-Toxoplasma antibodies and a negative ELISA for IgM antibodies. We believe that active focal retinitis in one eye and a focal chorioretinal scar in the fellow eye in congenital toxoplasmosis, as demonstrated in our patient, may be rare.

Absence of cellular responses to a putative autoantigen in onchocercal chorioretinopathy. Cellular autoimmunity in onchocercal chorioretinopathy.

PURPOSE: Onchocerciasis is a major cause of blindness in the developing world. An autoimmune pathogenesis for onchocercal chorioretinopathy was proposed after the identification of a recombinant Onchocerca volvulus antigen (designated Ov39) demonstrated immunologic crossreactivity with a component of the retinal pigment epithelium and other ocular tissues. The aim of this study was to determine whether patients with onchocercal chorioretinopathy have enhanced lymphoproliferative responses to Ov39 compared to those without chorioretinal disease. METHODS: Lymphocyte blastogenic assays were performed using peripheral blood mononuclear cells (PBMCs) from patients with and without evidence of chorioretinopathy. PBMCs were cultured with Ov39, and supernatant fluids from Ov39-stimulated PBMCs were used to determine levels of the cytokines, interferon-gamma, and interleukin-5. RESULTS: Lymphoproliferative responses to Ov39 were not enhanced in patients with onchocercal chorioretinopathy compared to those without clinical evidence of chorioretinal disease. CONCLUSIONS: A role for Ov39-specific cellular autoreactivity in the pathogenesis of onchocercal chorioretinopathy could not be demonstrated.

[Role of immunological factors in peripheral vitreo-chorioretinal dystrophies and macular ruptures of the retina]. / Izuchenie roli immunologicheskikh faktorov pri perifericheskikh vitreokhorioretinal'nykh distrofiiakh i makuliarnykh razryvakh setchatki.

The authors analyze the results of clinical and immunological examinations of patients with peripheral vitreo-chorioretinal dystrophies (PVCRD) and macular ruptures of the retina. No antibodies to S-AG were detected in the lacrimal fluid in 87.5% of patients with PVCRD without retinal defects. In patients with PVCRD with retinal defects antibodies to S-AG were detected in 70% of cases. These antibodies were absent in the patients with macular ruptures of the retina. In none of the patients were these antibodies detected in the blood serum. The levels of circulating immune complexes were normal in the patients PVCRD and increased in those with macular ruptures of the retina. These data permit a hypothesis on the development of local autoimmune reactions in PVCRD patients in response to the appearance of AG of the injured tissues.

Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy.

Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from Sierra Leone, West Africa using a two-step migration-inhibition factor assay. Patients were subdivided into three groups: (1) without ocular involvement (n = 10), (2) with ocular onchocerciasis limited to the anterior segment (n = 19), and (3) with onchocercal chorioretinopathy (n = 21). A group of endemic controls (n = 25) from Sierra Leone were also studied. The cellular immune response to concanavalin A (Con A) was measured to assess the general capacity of lymphocytes to respond to a mitogen. Four of 50 (8%) patients with onchocerciasis and four of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. A role for an antiretinal autoimmune mechanism in the pathogenesis of onchocercal chorioretinopathy, as studied with human S-antigen, IRBP, or crude retinal extract, could not be shown because the cellular response to these antigens did not differ in patients with or without onchocercal chorioretinopathy or in endemic controls.

Late developing lesions in birdshot retinochoroidopathy.

Birdshot retinochoroidopathy is characterized by depigmented spots radiating from the optic disk in association with mild vitritis, retinal vasculitis, and involvement of the optic nerve head. In two patients, we traced the long-term course of uveitis with vitritis, retinal vasculitis, and papillitis that resulted in the typical cream-colored spots of birdshot retinochoroidopathy after seven and eight years, respectively, of follow-up. These observations suggest that in long-standing inflammation of the retinal vasculature and uveal tract, the HLA-A29 antigen should be assessed, because the development of typical lesions of birdshot retinochoroidopathy may be delayed in some patients.

Association of birdshot retinochoroidopathy and HLA-A29 antigen.

In 1980 Ryan and Maumenee described a new clinical entity characterized by hypopigmented spots in a typical patterned distribution in association with vitritis and retinal vasculopathy leading to cystoid macular oedema and papilloedema. In a recent study of a large group of European patients (n = 102) with birdshot retinochoroidopathy, the importance of the different clinical manifestations and their diagnostic value were assessed. Data on HLA-A29 typing were obtained in 49 patients with birdshot retinochoroidopathy. We could confirm the high association between HLA-A29 and this disease, as found by Nussenblatt in 1982. In 47 of these patients (95.5%) the HLA-A29 antigen was present. This association is presently the highest HLA class I disease association reported with a relative risk of 224.35.

Severe retinochoroidopathy: variations of humoral and cellular immunity to S-antigen in a longitudinal study.

Ten patients with birdshot retinochoroidopathy, six with isolated retinal vasculitis and eight with Behçet's disease were treated with cyclosporine for one to three years. Autoantibodies to several retinal proteins, circulating lymphocyte subsets and cellular reactivity to S-antigen were evaluated repeatedly during this period. Autoantibody titers were similar in patients and in controls. However the serum content of antibodies to IRBP or S-antigen was lessened during inflammatory periods in some patients. In some sera, antibodies reacted with enzyme digested S-antigen preparations by immunoblot, whereas the same sera were negative for the native protein. A decrease of the CD4+ subpopulation of peripheral blood lymphocytes was associated with relapses of ocular inflammation in birdshot retinochoroidopathy. In this disease and in idiopathic retinal vasculitis, the positive lymphocyte stimulation test and basophil degranulation test with S-antigen were significantly most frequent in the period preceding a relapse of ocular inflammation. These tests could therefore be of predictive value for relapses occurring within the next few months.

[Vascular manifestations in birdshot chorioretinopathy]. / Les manifestations vasculaires dans la choriorétinopathie "birdshot".

The retinal vascular changes and complications are described in 121 patients with birdshot chorioretinopathy. The medical history in these patients did not reveal any relevant correlation with a systemic disorder, although vascular accidents and arterial hypertension in this group were rather high. The antigen HLA-A29 was present in 95.9% of the patients.