C. Terrada

Efficacy of interferon alpha in the treatment of refractory and sight threatening uveitis: a retrospective monocentric study of 45 patients

Aim: Severe uveitis is potentially associated with visual impairment or blindness in young patients. Therapeutic strategies remain controversial. The efficacy of interferon alpha-2a (IFN-α2a) in severe uveitis, refractory to steroids and conventional immunosuppressive agents, was evaluated. Patients and methods: Patients were included after a major relapse of uveitis following corticosteroids and immunosuppressants. IFN-α2a (3 million units three times a week) was administered subcutaneously. Efficacy was assessed by improvement in visual acuity, decrease in vitreous haze, resolution of retinal vasculitis and macular oedema, assessed by fundus examination and fluorescein angiography, and decrease in oral prednisone threshold. Results: 45 patients were included. Median age was 32.3 years (range 8–58) and sex ratio (F/M) was 0.66. Uveitis was associated with Behçet’s disease in 23 cases (51.1%) and with other entities in 22 cases (48.9%). Median duration of uveitis before interferon therapy was 34.9 months (range 3.4–168.7) and an average of 3.26 relapses following corticosteroids and immunosuppressants was noted. Uveitis was controlled in 82.6% of patients with Behçet’s disease and 59% of patients with other types of uveitis (p = 0.07). During a mean follow-up of 29.6 months (range 14–55), median oral prednisone threshold decreased significantly from 23.6 mg/day (range 16–45) to 10 mg/d (range 4–14) (p<0.001). Interferon was discontinued in 10 patients (22.2%) with Behçet’s disease and in four patients without Behçet’s disease. Relapses occurred in four and one cases, respectively. Conclusions: Interferon therapy appears to be an efficient strategy in severe and relapsing forms of Behçet’s disease but also in other uveitic entities. However, it seems to act more to suspend rather than cure the disease. Therefore, IFN-α2a may be proposed as a secondline strategy after failure of conventional immunosuppressants.

High prevalence of fastidious bacteria in 1520 cases of uveitis of unknown etiology.

The etiologic evaluation of uveitis is frequently unsuccessful when noninvasive methods are used. We conducted a prospective study to evaluate systematic screening for pathogens of uveitis. All patients with uveitis referred to the participating tertiary ophthalmology departments from January 2001 to September 2007 underwent intraocular and serum specimen collection. The standardized protocol for laboratory investigations included universal polymerase chain reaction (PCR)-based detection of any bacteria and mycoses, specific PCR-based detection of fastidious (difficult-to-grow) bacteria and herpes viruses, and culture of vitreous fluid. Sera were tested for fastidious bacteria. Among the 1321 included patients (1520 specimens), infection was diagnosed in 147 (11.1%) patients: 78 (53%) were caused by fastidious bacteria that included spirochetes, Bartonella species, intracellular bacteria (Chlamydia species, Rickettsia species, Coxiella burnetii), and Tropheryma whipplei; 18 by herpes viruses; and 9 by fungi. Bartonella quintana, Coxiella burnetii, Paracoccus yeei, Aspergillus oryzae, and Cryptococcus albidus were found to be associated with uveitis for the first time, to our knowledge. We recommend applying a 1-step diagnostic procedure that incorporates intraocular, specific microbial PCR with serum analyses in tertiary centers to determine the etiology of uveitis. Abbreviations: ACP = anterior chamber paracentesis, EBV = Epstein-Barr virus, ELISA = enzyme-linked immunosorbent assay, HIV = human immunodeficiency virus, HSV = herpes simplex virus, PCR = polymerase chain reaction, TP-PA = Treponema pallidum particle agglutination test, VDRL = Venereal Disease Research Laboratory test.

Maculopathy in uveitis of juvenile idiopathic arthritis: an optical coherence tomography study

Aim: The aim of this study was to examine the frequency and characteristics of macular lesions observed in juvenile idiopathic arthritis (JIA) uveitis, using optical coherence tomography (OCT). Methods: In this cross-sectional study, 38 consecutive patients were recruited from a tertiary referral center in uveitis. All eyes with JIA uveitis underwent complete ophthalmic examination including OCT 3. Exclusion criterion was the inability to obtain OCT scans. Flare and visual acuity were also analysed by using linear regression. Results: We analysed foveal thickness (FT) and central foveal thickness (CFT), using software mapping, to describe macular lesions in 61 eyes. Maculopathy was observed in 51 eyes (84%) compared with 12% in the literature (p<0.0001) and comprised four types: perifoveolar thickening in 45 eyes (74%), macular oedema in 29 eyes (48%), foveal detachment in 11 eyes (18%) and atrophic changes in six eyes (10%). Only four eyes did not demonstrate any lesion. Conclusions: Among children with JIA uveitis, macular involvement is frequent and characterised by perifoveolar thickening and serous retinal detachment. OCT is a non-invasive instrument. It can easily identify this maculopathy, which could impair visual function, and require therapeutic intensification.

Azathioprine in severe uveitis of Behçet's disease.

To investigate the efficacy and tolerance of azathioprine in severe uveitis related to Behçets disease (BD).

Intravitreal bevacizumab as first local treatment for uveitis‐related choroidal neovascularization: long‐term results

Purpose:  To report long‐term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis.

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

In many clinical cases, uveitis develops secondary to an infection. This could result from peripheral activation followed by ocular penetration and reactivation of T cells specific for microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis, we developed a new mouse model based on stable retinal expression of influenza virus hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro or in vivo. Intraocular inflammation was clinically and histologically observed in all animals within 15 days. The ocular infiltrate was composed mostly of macrophages and HA-specific T cells with a proinflammatory cytokine profile. Depletion of CD4+CD25+ regulatory T cells exacerbated the disease, whereas HA-specific CD4+CD25+ T cells given i.v. controlled the disease. This novel model should allow to better study the pathophysiology and therapeutic of uveitis.

Ocular modifications in a young girl with cryopyrin-associated periodic syndromes responding to interleukin-1 receptor antagonist anakinra

An 8-year-old patient with genetically confirmed chronic infantile neurological cutaneous and articular syndrome was treated with interleukin-1 receptor antagonist, anakinra. She initially presented with recurrent episodes of fever, rash, chronic fatigue, frequent headaches, ocular involvement (corneal infiltrate and papillary edema), and permanent increased biologic inflammatory markers. Following treatment with anakinra, all symptoms and inflammation resolved. Ophthalmologic signs normalized. This ophthalmologic description (optic nerve and cornea) has never been illustrated, even if ocular affections are classic in the cryopyrin-associated periodic syndromes.

Cataract surgery with primary intraocular lens implantation in children with uveitis: Long-term outcomes

PURPOSE: To report long‐term outcomes of cataract surgery with primary posterior chamber intraocular lens (IOL) implantation in children with chronic uveitis. SETTING: Department of Ophthalmology, Pitié‐Salpêtrière Hospital, Paris, France. DESIGN: Case series. METHODS: This case series comprised patients younger than 16 years with chronic uveitis who underwent phacoemulsification with primary implantation of a heparin surface‐modified poly(methyl methacrylate) posterior chamber IOL in the capsular bag. The intraocular inflammation was fully controlled for at least 3 consecutive months before surgery in all cases. The main outcome measures were final corrected distance visual acuity (CDVA), postoperative inflammation, complications, and level of immunosuppressive treatment. RESULTS: Twenty‐two eyes of 16 children (7 girls, 9 boys; median age at surgery 9.5 years old) were included. Underlying uveitic entities were juvenile idiopathic arthritis in 9 patients; idiopathic uveitis in 4; and Behçet disease, sarcoidosis, and varicella zoster‐associated uveitis in 1 patient each. The final CDVA was 0.3 logMAR or better in all cases. Postoperative complications included posterior capsule opacification requiring laser capsulotomy in 2 eyes, glaucoma in 4 eyes, and cystoid macular edema/macular dysfunction in 3 eyes. The mean dose of oral prednisone was 29.5 mg/day preoperatively and 8.13 mg/day at the last follow‐up. The median follow‐up was 6 years (range 5 to 19 years). CONCLUSION: The results indicate that uveitis is not a formal contraindication to primary IOL implantation in the management of pediatric cataract surgery in cases with full control of intraocular inflammation. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Uveitis: an emerging clinical form of Bartonella infection

A few reports have now established that the cat scratch disease agent Bartonella henselae is responsible for uveitis [1]. Bartonella grahamii has also been recognized as being responsible for uveitis [2]. However, the prevalence of Bartonella uveitis remains poorly known, as is the potential role of other Bartonella species. Prospective evaluation of a standardized laboratory protocol for the diagnosis of uveitis of unknown aetiology [3] showed that Bartonella species were responsible for most cases of bacterial uveitis. Prominent clinical features and laboratory diagnosis data of this large series are reported herein. This study was approved by the Ethics Committee of our institution; patients with a known aetiological diagnosis and patients with ophthalmological features pathognomonic of an aetiology, such as toxoplasmosis, were not eligible. A questionnaire was used for the collection of data, and was anonymized before the study according to French law. Informed consent for inclusion was obtained from patients and parents or legal guardians of children (i.e. age <18 years). Uveitis was classified according to the international uveitis study group definition and classification. Five millilitres of serum and ocular fluid were collected aseptically, by anterior chamber paracentesis or vitreous tap ⁄ vitrectomy. Serum was tested for the presence of antibody against B. henselae Houston and Marseille serotypes, Bartonella quintana and B. grahamii using microimmunofluorescence and Western blot [4]. After lysis, nucleic acids were isolated using the tissue kit and the Magna-Pure apparatus, according to the instructions of the supplier (Roche Applied Science, Indianapolis, IN, USA). Intra-ocular specimens from deceased patients without infection from the Marseilles area as well as water and mix samples were used as negative controls. One negative control was used for eight specimens, and any false-positive control annulled the validity of the assay. A nested PCR targeting the Bartonella hbpE gene, using primer pair 5¢-GAGAGTGCTTCACCTAAATAG-3¢ and 5¢-CCACCAATCTGTCCTCCAAA-3¢, was performed. The diagnosis of Bartonella uveitis was considered as definite if: (i) positive PCR with an identifying sequence was obtained from ocular fluid; and (ii) the antibody level was ‡1 : 100 by microimmunofluorescence or there were ‡2 specific bands in Western blot for Bartonella spp. Between January 2001 and April 2008, 1520 intra-ocular and serum specimens collected from 1417 patients were analysed. Bartonella spp. infection was diagnosed in 31 (2.6%) patients, by specific molecular testing of intra-ocular specimens only in four patients, and by Western blot only in ten patients. Uveitis was due to B. henselae in 17 patients, B. quintana in seven patients, B. grahami in four patients, and undetermined Bartonella spp. in three patients (Table 1). All cases of B. henselae uveitis were due to the Houston genotype as determined by sequencing PCR products or by Western blot analysis. In our series, Bartonella spp. ranked second after spirochaetes among the fastidious pathogens responsible for uveitis. Characteristic stellar retinitis was found in nine of 31 (29%) patients, but clinical features were otherwise non-specific, with uveitis being posterior in 18 of 31 (58%) patients, anterior in nine of 31 (29%), intermediate in two of 31 (6.5%), and panuveitis in two of 31 (6.5%). Patients presented with non-granulomatous uveitis in 18 of 31 (58%) cases and granulomatous uveitis in 13 of 31 (42%) cases. Contacts with animals were notable in 11 of 31 (35.5%) patients. In most patients, the diagnosis was made by Corresponding author and reprint requests: Michel Drancourt, URMITE, Faculte de Medecine, 27 Boulevard Jean Moulin, 13385, Marseille cedex 9, France E-mail: michel.drancourt@univmed.fr

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

Purpose: To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis. Design: Retrospective observational case series. Methods: Clinical data from patients who present familial JIA-associated uveitis are described and possible genetic influence in disease etiology is reviewed. Results: Two sisters, 6- and 7-year-old, developed bilateral anterior uveitis related to oligoarticular JIA. Arthritis in both began by the age of 18 months; uveitis developed simultaneously in one of them and less than one year after arthritis in the other one. Both received topical and systemic treatment to control the ocular disease. Glaucoma occurred in both cases and bilateral cataract in one case. In the other family, a 2-year-old girl developed unilateral uveitis in the context of oligoarticular JIA which was diagnosed by 1-year-old. The disease became soon bilateral and she received topical and systemic immunosuppressive treatment. Her mother suffered from bilateral anterior uveitis associated to oligoarticular inflammatory disease during her infancy, later diagnosed as JIA-associated uveitis. Conclusions: Familial cases of JIA uveitis, although not very common, support the possible role of genetic influence in the pathogenesis of the disease, with horizontal and vertical inheritance being possible. The evolution of ocular disease is similar to the non-familial cases, except for an earlier age of onset.