Bilateral Posterior Uveitis Research Articles

The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.

Birdshot chorioretinopathy (BSCR) is a bilateral chronic intraocular inflammation or posterior uveitis that preferentially affects middle-aged Caucasians. BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis, and the extraordinary feature that virtually all patients are HLA-A29 positive. Its pathophysiology is still poorly understood. BSCR is the strongest documented association between HLA and disease in humans, which makes it an excellent model for studying the underlying immuno-genetic mechanisms of HLA class I-associated diseases. Although the association with HLA-A29 suggests that it is directly involved in the presentation of peptide antigens to T cells, the exact contribution of HLA-A29 to the pathophysiology of BSCR remains enigmatic. This article revisits the HLA-A29 peptidome using insights from recent studies and discusses why HLA-A29 can be considered a canonical antigen presenting molecule. The first genome-wide association study facilitated novel concepts into a disease mechanism beyond HLA-A29 that includes strong genetic predisposition for the ERAP2 gene that affects antigen processing for HLA class I. Furthermore, patients manifest with pro-inflammatory cytokine profiles and pathogenic T cell subsets that are associated with IL-17-linked inflammation. We are beginning to understand that the underlying biology of BSCR comprises various pathologic aspects branched into multiple molecular pathways. We propose to employ Systems Medicine to reveal their dynamic interplay for a holistic view of the immunopathology of this intriguing archetypal HLA class I-associated disease.

Correlation between clinical signs and optical coherence tomography with enhanced depth imaging findings in patients with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BCR) is a bilateral posterior uveitis that typically requires aggressive therapy to prevent loss of vision. Clinical signs of disease activity may be subtle and visual acuity is often preserved despite significant loss of visual function. Optical coherence tomography with enhanced depth imaging (OCT-EDI), a new technology that allows visualization of structures posterior to the retinal pigment epithelium, may be a useful tool to monitor disease activity in these patients. To determine the correlation between symptoms and signs of disease activity in BCR and specific findings on OCT-EDI. Retrospective medical record review of 14 patients treated for BCR in the uveitis clinic at Northwestern University. All patients underwent OCT-EDI (58 scans). Clinical symptoms of photopsias/vibrating vision and signs of macular edema, vitreous haze, and retinal vasculitis were graded; a second grading scale was developed for the evaluation of OCT-EDI. Individual scans of each eye of each patient at each point were graded in a masked fashion. Optical coherence tomography with EDI in BCR. Spearman rank correlation of clinical measures to OCT-EDI measures. The most frequent score in each clinical category was 0 (inactive). In those BCR patients with symptoms (21 eye examinations), the subjective complaint of photopsias/vibrating vision was associated with the objective finding of suprachoroidal fluid on OCT-EDI (P = .003), and the frequency and severity of photopsias correlated with the thickness of the fluid band (Pearson product moment correlation, 0.39). Two of the clinical markers of disease activity measured in this study (vasculitis and vitreous haze) also showed a significant Spearman rank correlation with the presence and amount of suprachoroidal fluid on OCT-EDI (vasculitis, 0.45 [P < .001]; vitreous haze, 0.59 [P < .001]). The presence of suprachoroidal fluid on OCT-EDI appears to correlate with the subjective complaints of photopsias in patients with BCR and other more easily assessed clinical features such as vasculitis and vitreous haze. Optical coherence tomography with EDI may be a useful tool for objective monitoring of BCR.

Birdshot retinochoroidopathy.

Birdshot retinochoroidopathy (BSRC) is an uncommon, but well-characterized chronic, bilateral posterior uveitis, which is uniquely associated with the human leukocyte antigen-A29 phenotype. The disease presents predominantly in middle-aged Caucasian females who complain of blurred vision, floaters, photopsias, paracentral scotomas and nyctalopia. While autoimmune mechanisms are thought to play an important role in the pathogenesis of BSRC, its etiology remains unknown. Important questions remain in our understanding of BSRC with respect to its pathogenesis, epidemiology, optimal treatment, and prognosis, including the determinants of remission and relapse, as well as the best strategy for monitoring disease activity, progression and response to therapy with electroretinographic and psychophysical testing, established and emerging imaging modalities, and peripheral cytokines profiles.

FRI0354 Efficacy of infliximab in the treatment of sight-threatening uveitis in behçet’s disease

BackgroundDespite intensive immunosuppressive therapy, permanent loss of vision resulting from relapsing ocular inflammation occurs frequently in Behçet’s disease. Since tumor necrosis factor (TNF) have a pathogenic role in Behçet’s uveitis,...

Vision‐related quality of life in patients with birdshot chorioretinopathy

Dear Editor, Birdshot chorioretinopathy (BSCR) is a potentially blinding chronic form of bilateral posterior uveitis. Despite intensive anti-inflammatory therapies, patients may exhibit a slow decline in visual functioning including the central visual acuity and contrast sensitivity (Shah et al. 2005). Here, we ascertain the vision-specific quality of life (QOL) in patients with BSCR and study the associations between QOL and treatment modalities. The study was performed in accordance with the Declaration of Helsinki and with the approval of the local institutional review board. We included 127 consecutive patients with BSCR from the department of ophthalmology of the University Medical Centre Utrecht and the Eye Hospital Rotterdam, the Netherlands. Diagnosis was based on research criteria established by an international consensus conference (Levinson et al. 2006) and included fluorescein angiography. All included patients were HLA-A29 positive. The Dutch translation of the NEI Visual Function Questionnaire (VFQ)-25 was sent to all subjects (Mangione et al. 2001). A total of 105 (83%) patients (median age 59.5; range 28–83 years) completed questionnaires, which were returned after obtaining informed consent. The reasons for not responding included death (n = 4) or no interest in participation (n = 18). Gender, age, duration of uveitis, previous treatment and best-corrected visual acuity (BCVA) were registered for all subjects (mean binocular visual acuity; LogMAR 0.82 ± 0.24; range 0.05–1.0). Previous treatment was divided into three groups: (i) no systemic treatment (26 patients, 25%), (ii) systemic corticosteroids, but no other immunosuppressive drugs (15 patients, 14%), and (iii) immunosuppressive drugs occasionally in combination with systemic corticosteroids (64 patients, 61%). A p-value of 0.0045 or less was accepted as indicating statistical significance, using Bonferroni correction. The median NEI VFQ-25 composite score for patients with BSCR was 75.9, and median subscale scores ranged from 60 for general health to 91.7 for social functioning and dependency (Table 1). There was no difference in NEI VFQ-25 composite or subscales scores between the various treatment categories (Kruskal–Wallis test, p = 0.473). The composite scores were related to BCVA (Spearman correlation, p = 0.003), but not related to age (p = 0.6) or duration of uveitis (p = 0.8). The BCVA was not different between the treatment categories (p = 0.289). All correlations between the NEI VFQ-25 subscale scores and BCVA were significant, except for ocular pain (p = 0.878). BSCR has a high impact on vision-related QOL. VFQ-25 scores were associated with visual acuity, but no difference in VFQ-25 scores or BCVA was observed among the different treatment regimens and between treated and not treated patients. Our NEI VFQ-25 subscale score results are in the same range of those found in a previous cohort of BSCR (Levinson et al. 2009) and a recent study of vision-related QOL in noninfectious ocular inflammatory disease (Qian et al. 2012). The authors of the latter study stated that low composite VFQ-25 score was a predictor of depression, which they found was associated with the use of corticosteroids and antimetabolites. In this study, we did not assess depression specifically; however, the median composite and mental health scores were lower in the group of patients treated with systemic corticosteroids compared with the other groups (Table 1). The design of our study does not allow the evaluation of specific treatment efficacy because the treatment regimens were not random. Future randomized studies on the effect of different immunosuppressive treatment regimes and visual outcomes in BSCR are warranted.

Human herpes virus-6 as a cause of recurrent posterior uveitis in a HIV-positive patient.

To report a case of bilateral recurrent posterior uveitis caused by human herpes virus-6 (HHV-6) in a human immunodeficiency virus-positive individual. Comprehensive ophthalmic examination, including imaging with optical coherence tomography, fluorescein and indocyanine green angiography, and adequate laboratory tests were performed. A human immunodeficiency virus-positive patient without any AIDS defining condition, with a history of recurrent bilateral posterior uveitis referred to us with the diagnosis of retinal detachment. Vitreous polymerase chain reaction detected an aberrant band for herpes viruses, which proved to be human herpes virus-6 by repeated polymerase chain reactions. Serum antibodies titer was positive for human herpes virus-6. The patient responded well to antiviral therapy with valacyclovir. This is the first case of human herpes virus-6-related bilateral posterior uveitis in a human immunodeficiency virus-positive individual without clinical manifestations of AIDS.

Necrotic retinal pigment epithelium in toxoplasmic retinochoroiditis

Editor, We read with interest Belfort and colleagues’ clinicopathological report on a case of toxoplasmic retinochoroiditis, published in Acta Ophthalmologica (Belfort et al. 2008). The authors describe the histopathological findings of an enucleated globe of a 66-year-old immunosuppressed man with severe bilateral posterior uveitis that had progressed despite antiviral therapy for presumed cytomegalovirus retinitis. This article illustrated well the role of histopathological examination and immunohistochemistry in establishing definitively the aetiology in these challenging cases. However some of the authors’ histopathological observations deserve further comments. The authors stated that, in addition to the necrotizing retinitis and the granulomatous inflammation of the choroid, ‘necrosis of Bruch’s membrane’ might be a distinctive feature of toxoplasmic retinochoroiditis. However, histopathologically such a term is a misnomer. Necrosis is the morphological expression of cell death and is characterized by protein denaturation, loss of energy producing mechanisms, enzymatic cellular digestion and often a secondary inflammatory response (Spencer 1996). Being essentially an acellular structure, made up of the basement membranes of the retinal pigment epithelium (RPE) and of the choriocapillaris in each side, and of a core elastic layer surrounded by two collagenous zones (Garron 1963), Bruch’s membrane may undergo secondary pathological changes but not necrosis, and this term should be avoided. The secondary changes in Bruch’s membrane reflect the involvement of RPE and/or of choriocapillaris endothelium. RPE necrosis is shown nicely in their Fig. 1E (Belfort et al. 2008), and has been recognized not only in cases of toxoplasmic retinochoroiditis (Rao & Font 1977) but also in other necrotizing retinites secondary to mycobacteria, fungi, viruses and even in primary retinal lymphoma (Spencer 1996; Rao et al. 2006). Finally, according to the authors, the involvement and eventual disruption of Bruch’s membrane might justify the occurrence of secondary granulomatous inflammation of the choroid in toxoplasmic retinochoroiditis. Nevertheless this is unlikely, because in many of the entities listed earlier, secondary inflammation of the choroid occurs despite an uninterrupted Bruch’s membrane (Spencer 1996). We congratulate Belfort and colleagues on their interesting article, emphasizing the role of histopathology on the aetiological diagnosis of these complex cases.

Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant

PurposeTo report our experience with dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA) in noninfectious posterior uveitis.MethodsA retrospective chart review of patients with noninfectious uveitis treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including signs of inflammatory activity, visual acuity, fundus photography, fluorescein angiography, optical coherence tomography, and tolerability of the implant were assessed.ResultsSix eyes of 4 consecutive patients treated with a total of 8 dexamethasone 0.7 mg sustained-release intravitreal implants for posterior noninfectious uveitis were included. Two patients presented with unilateral idiopathic posterior uveitis; 2 patients had bilateral posterior uveitis, one secondary to sarcoidosis and the other to Vogt-Koyanagi-Harada syndrome. All eyes showed clinical and angiographic evidence of decreased inflammation following implant placement. Mean follow-up time post-injection was 5.25 months. Four eyes received 1 and 2 eyes received 2 Ozurdex implants during the follow-up period. The duration of effect of the implant was 3 to 4 months. No serious ocular or systemic adverse events were noted during the follow-up period.ConclusionsIn patients with noninfectious posterior uveitis, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option for controlling intraocular inflammation.

Drug-induced tubulointerstitial nephritis and uveitis syndrome with posterior uveitis resembling acute posterior multifocal placoid pigment epitheliopathy.

To report the occurrence of acute posterior multifocal placoid pigment epitheliopathy (APMPPE)-like posterior uveitis as part of the ocular manifestation of tubulointerstitial nephritis and uveitis (TINU) syndrome. A 54-year-old previously healthy woman received oral ibuprofen and dipirone because of high fever and malaise. Three days after being started on this treatment, she developed bilateral posterior uveitis resembling APMPPE accompanied by anterior segment inflammation in the context of acute renal nephritis and maculopapular skin rash probably related to drug exposure. The patient was hospitalized because of acute renal failure and received support therapy and topical steroids in both eyes. A renal biopsy was not performed (based on good clinical response), but she fulfilled the clinical criteria of acute interstitial nephritis and TINU. Although her renal and ocular functions improved in the first week, she needed to be readmitted days later because of fever and generalized edema and received steroid pulse therapy. Fluorescein angiography was consistent with an APMPPE-like pattern and optical coherence tomography showed neither macular edema nor subretinal fluid. The ocular picture improved during the following weeks with fundus changes resembling those of APMPPE. Although anterior uveitis is considered the typical ocular component of TINU syndrome, posterior uveitis resembling APMPPE may also be its ocular manifestation.

The present role of corticosteroids in uveitis

AbstractCorticosteroids are the most widely used anti‐inflammatory and immunosuppressant drugs in ophthalmology in general, and remain the mainstay of therapy for patients with uveitis.An infectious etiology for intraocular inflammation should be adequately excluded or appropriately covered with anti‐infectious therapy before administration of corticosteroid therapy. Topical corticosteroids alone are usually effective in the management of anterior uveitis and have little activity against intermediate or posterior uveitis. Ocular adverse effects of topical steroid therapy mainly include ocular hypertension and cataract. The use of periocular steroid injections (subconjunctival, anterior or posterior subtenon, orbital floor) are important modalities in the management of anterior uveitis refractory to topical treatment and intermediate or posterior uveitis, particularly unilateral cases. Systemic corticosteroids remain the initial drug of choice for most patients with severe bilateral intermediate or posterior uveitis. Therapy is initiated with 1.0 to 2.0 mg/Kg of oral prednisone or prednisolone as a single morning dose, followed by a slow taper. Use of intravenous pulse steroid therapy is an important option in acute, severe, bilateral posterior segment inflammation. In several cases, the level of systemic steroid required to control the inflammation is too high and unacceptable. Immunosuppressive drugs as steroid‐sparing agents are indicated is such cases. Intravitreal injection of triamcinolone acetonide and slow‐release intraocular devices are therapeutic options that can be used in selected uveitis cases refractory to conventional therapy and biologic agents.

Bilateral retinochoroiditis caused by an atypical strain of Toxoplasma gondii

Background:A 53-year-old man presented with an acute bilateral posterior uveitis with extensive necrotising retinochoroiditis but without chorioretinal scarring. A thorough workup did not reveal any underlying disease. The possibilities of...

Antimicrobial treatment of presumed ocular tuberculosis

Abstract Purpose: Uveitis secondary to a tuberculosis is rarely reported, even in a tertiary a care center. The prevalence of tuberculosis is low in Western Europe and its microbiological identification is difficult. However, anti tuberculosis treatment may be useful when the diagnosis of tuberculosis is presumed. Methods: The clinical records of patients with suspected tuberculosis uveitis referred to the Ophthalmology Department of the Grenoble University, between January 2005 and January 2007 were retrospectively analyzed. Patients were included in this series if they received a specific antituberculosis treatment. Results: This series included 10 patients (3M/7F, mean age 54.1). The clinical features of ocular inflammation were: bilateral panuveitis, episcleritis, bilateral posterior uveitis, and pars planitis. Tuberculin skin test, chest computerized tomography, BK sputum, and internal medicine consultation were performed for all patients. The diagnosis of presumed tuberculosis was based upon: history, thoracic imaging, and tuberculin skin test. None had extra‐ocular symptoms. Sputum cultures were negative, 2 adenopathy biopsies confirmed the diagnosis. Nine patients received specific antituberculosis therapy, without systemic steroid therapy. All of them improved; no relapse occurred after 1 to 2 years after the end of therapy. In one case, tuberculosis specific therapy allowed to taper the systemic steroid therapy. Conclusions: The diagnosis of uveitis associated with tuberculosis is difficult since it depends on a spectrum of indirect signs. Bacteriological identification is rarely obtained. In presumed ocular tuberculosis, antituberculosis therapy may be useful to control intraocular inflammation, with or without steroid therapy.

Long-term efficacy of infliximab in refractory posterior uveitis of Behcet's disease: a 24-month follow-up study

To evaluate the long-term efficacy and safety of infliximab in patients with Behçet's disease (BD) and refractory bilateral posterior uveitis, and to assess the proportion of relapse-free subjects through months 12 and 24. Open-label, multicentre, 24-month, prospective, follow up study on 12 consecutive patients with BD and refractory posterior uveitis who had failed at least one immunosuppressive drug. At baseline patients received prednisolone 1 mg/Kg/day with rapid tapering and nine infliximab infusions (5 mg/kg) over a 12-month period. Non-responders after the third infusion withdrew from the study. Patients were evaluated for ocular inflammation degree, visual acuity (VA), number of ocular attacks and incidence of adverse events (AEs). At 12-month visit, 9/12 (75%) patients achieved a complete remission with no relapse during the treatment period. All had a dramatic improvement of ocular inflammation after the first infusion, six were in complete remission after three infusions, and three after four. All these patients suspended corticosteroids at week 22. At 24-month visit, seven out of nine (78%) were still in remission. Mean VA improved from 0.2 +/- 0.6 to 0.5 +/- 0.2 (P < 0.001), and ocular attacks dropped from 40 in the year before therapy to 5 after infliximab cessation (P < 0.001). One patient had a partial remission with two relapses during treatment, and 2/12 (17%) patients showed no improvement. Infliximab was well tolerated with no serious AEs. Infliximab is rapidly effective and safe in a high proportion BD patients with refractory posterior uveitis, and may be helpful to prevent recurrences.

Malignant uveitis masquerading a lymphocytic lymphoma

A multitude of diseases can present as posterior bilateral uveitis. In most cases, the cause of pericardial effusion can be determined, but in some instances, the cause is not apparent even after makinga systematic and complete diagnostic evaluation. We report here an unusual case of a patient who had a B-cell lymphocytic lymphoma, which presented as bilateral posterior uveitis. The diagnosis by biopsy is described, as is the role of multiple test in the diagnosis of bilateral uveitis.

Infliximabe no tratamento de uveíte posterior refratária em paciente com doença de Behçet

Perda visual permanente, resultante de inflamacao ocular recidivante, ocorre frequentemente em pacientes com doenca de Behcet, apesar de tratamento imunossupressor cronico e intensivo. Os autores relatam o caso de um paciente masculino, com 35 anos de idade, apresentando uveite posterior, cronica e bilateral, refrataria ao tratamento com corticosteroides e imunossupressores. O tratamento com infliximabe mostrou um efeito benefico na uveite desse paciente.

Corticosteroid Treatment for Melanoma-Associated Retinopathy

Visual disturbance in the course of melanoma is rare. Specific localized metastases and drug toxic effects are frequently the cause. Recognition of a retinopathy raises several questions when the diagnosis of melanoma-associated retinopathy (MAR) can be confirmed. Descriptions of such patients in dermatologic literature are rare and deserve attention because therapeutic decisions are mandatory. A 70-year-old woman had a first melanoma in 1985 and a second primary melanoma in 1994. Axillary lymph node involvement occurred in November 2000, leading to surgery and chemotherapy. In December 2001, she had sudden bilateral visual loss, with shimmering blobs of color and flickering photopsias. Computed tomography and cerebral magnetic resonance imaging ruled out localized tumor on the eyes or optic nerves or evolution of disease. Ophthalmologic examination revealed a bilateral posterior uveitis, with hyalitis and progressive destruction of retinal pigment. The electrophysiologic data confirmed the diagnosis of MAR. Symptoms improved after systemic corticosteroid therapy, with no relapse after tapering doses despite worsening of melanoma. As a rare paraneoplastic visual syndrome possibly leading to blindness, MAR is characterized by bipolar cell involvement without photoreceptor cell impairment. Also, MAR is linked to the presence of autoantibodies directed against melanoma antigens that cross-react with the rod bipolar cells of the retina. Corticosteroid therapy is rarely beneficial. Our case of MAR is noteworthy because it involved a woman, was associated with an uveitis, and improved with corticosteroid therapy.

Birdshot retinochoroidopathy: immunopathogenesis, evaluation, and treatment.

Birdshot retinochoroidopathy (BSR) is a bilateral posterior uveitis. A putative organ-specific autoimmune disease, it is strongly associated with the HLA-A29 allele, and understanding the immunopathogenesis of BSR is of great interest. The clinical features include minimal anterior uveitis, vitritis, retinal vasculitis, cystoid macular edema, and distinctive hypopigmented choroidal lesions. Findings on electrophysiology studies and angiography have implications for understanding the pathophysiology of the disease, and may be useful for following the course of BSR and the response to therapy in individual patients. The decision to initiate therapy can be difficult, but corticosteroids and immunosuppressive agents are often used.

Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy

Intravenous polyclonal immunoglobulin (IVIg) treatment has been successfully used in a number of autoimmune conditions. Birdshot retinochoroidopathy (BRC) is a bilateral autoimmune posterior uveitis which, in its progressive form, frequently requires immunosuppressive therapy. We report a clinical study aimed at determining the tolerance and efficiency of IVIg treatment in patients with active BRC. The study was conducted in an open manner. Eighteen patients were included. The initial visual acuity (VA) was =20/30 in 26 eyes, 20/25 in five eyes, and 20/20 in five eyes. IVIg was given as sole treatment at 1.6 g/kg every four weeks for six months, followed by injections of 1.2-1.6 g/kg at six to eight-week intervals. The mean follow-up was 39 months, ranging between 12 and 53 months. The results showed that the final VA of the 26 eyes with an initial VA of =20/30 was increased by two lines or more in 14 eyes (53.8%) and decreased in two (7.7%). Of the five eyes with an initial VA of 20/25, four had improved to 20/20 and one remained stable. Of the five eyes with an initial VA of 20/20, four remained stable and one deteriorated to 20/25. When present, macular edema was improved in half of the eyes on fluorescein angiography. Benign side effects were observed in 12 patients: moderate transient arterial hypertension (7), headache (6), eczematous lesions (6), and hyperthermia (4). The results suggest that IVIg may represent a safe alternative therapy for patients with BRC.

Uveite e dermodespigmentação (Síndrome de Vogt-Koyanagi- Harada) em cães Akita

A síndrome de Vogt-Koyanagi-Harada, caracterizada pela associação de uveite e alteraçõe cutaneas e de meninge, de causa desconhecida é bastante estudada na oftalmologia humana. Foi primeiro descrita no Japão uma síndrome semelhante em cães da raça Akita, sendo que relatos em outras raças e outrosçpaíses como Canadá, Estados Unidos e Inglaterra foram feitos posteriormente. Descrevemos pela primeira vez no Brasil esta associação úveo-dermatológica em 21cães da raça Akita. Caracterizada por uveíte e despigmentação ao redor das pálpebras, lábios, narina e escroto podendo haver ulceração com formação de crostas nestas regiões. A administração de altas doses de corticosteróides é o tratamento de eleição.

The antineutrophil antibody in uveitis.

Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular single/repeated rather than nonrecurrent uveitis was associated with a positive test. Three groups of patients seem more likely to have positive tests: those with bilateral chronic posterior uveitis; a group with an anterior uveitis which is single/repeated who were younger than 46 at disease onset and had isolated eye disease; and an older group, aged 60 years or more at onset, with single/repeated uveitis and systemic features.