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to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features.This is a multicenter, retrospective case series. Patients under biologic therapy were included if they developed uveitis for the first time or experienced intraocular inflammation which was different in location or laterality to previous inflammation.Sixteen patients were identified. The underlying disorders included ankylosing spondylitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Behçet's Disease. The biologic agents associated with a first episode of uveitis (n = 11) or with a new recurrence of uveitis (n = 5) were etanercept, adalimumab, abatacept, infliximab, and golimumab. Sarcoidosis based on bihilar lymphadenopathy, other computer tomography-findings, or biopsy was diagnosed in five patients under therapy with etanercep, adalimumab, and abatacept. Additionally, seven patients developed clinical changes in their uveitis pattern, suggesting sarcoid uveitis.Biologic treatment-induced uveitis often presents as granulomatous disease.

To provide an overview of biologics that are used to treat noninfectious uveitis, including their different targets, modes of actions, and indications.A review of recent and well-established literature was used to present the biochemical and pathophysiological background of biologics and to provide an account of evidence-based decision making for their use, not only in noninfectious uveitis in general, but with special regard to indications for their use in particular types of uveitis.Extensive clinical data for adalimumab shows that it is currently the only approved biologic for the treatment of uveitis. However, there is sufficient evidence to argue that many other biologics, notably TNF-α inhibitors, certain Interleukin inhibitors, Interferons, and B cell and T cell inhibitors, are also suitable for use in uveitis.Biologics have revolutionized the treatment of noninfectious uveitis and are now considered indispensable. They are used in cases of insufficient response to or intolerance of conventional immunosuppressive agents. However, they can also be indicated as a first-line therapy for certain types of uveitis (e.g., Behçet's disease). TNF-α inhibitors are the most commonly used biologics in the treatment of uveitis.Ziel dieser Zusammenfassung ist das Vermitteln einer Übersicht zu den verschiedenen Ansatzpunkten, Wirkmechanismen und Indikationen diverser Biologika, die bei der Therapie der nichtinfektiösen Uveitis zum Einsatz kommen.Etablierte sowie aktuelle Literatur wurden herangezogen, um die biochemischen und pathophysiologischen Grundlagen sowie eine evidenzbasierte Empfehlung zum Therapieeinsatz verschiedener Biologika bei nichtinfektiöser Uveitis allgemein und bei speziellen Uveitisentitäten darzulegen.Für viele Biologika, hier nennenswert TNF-α-Inhibitoren, einige Interleukininhibitoren, Interferone sowie B- und T-Zell-Inhibitoren, liegen mittlerweile gute Daten vor, was ihren Einsatz in der Uveitistherapie mehr als rechtfertigt. Dies trifft insbesondere für den TNF-α-Inhibitor Adalimumab zu, welcher der einzig zugelassene Vertreter für diese Indikation unter den vorgestellten Biologika ist.Die Biologika haben die Behandlung der Uveitis revolutioniert und sind aus der aktuellen Therapie der intraokularen Entzündung nicht mehr wegzudenken. Biologika werden bei Ineffektivität oder Unverträglichkeit konventioneller immunsuppressiver Medikamente empfohlen, aber auch bei der Therapie von schwerwiegenden Uveitisformen (z. B. Morbus Behçet). Die TNF-α-Inhibitoren sind die am häufigsten verwendeten Biologika bei Uveitis.

ZusammenfassungDas Behçet-Syndrom (BS) ist eine entzündliche Systemerkrankung, die mit multiplen Organmanifestationen einhergeht. Häufigste Krankheitssymptome sind orale Aphthen, genitale Ulzerationen, Hauteffloreszenzen und Augenmanifestationen. Die Diagnose des Behçet-Syndroms wird anhand klinischer Symptome gestellt. Typische okuläre Präsentation beim Behçet-Syndrom ist die rezidivierende nicht granulomatöse Panuveitis mit okklusiver retinaler Vaskulitis. Früher waren systemische Steroide und konventionelle Immunsuppressiva die einzige therapeutische Option beim Behçet-Syndrom. Unter dieser Therapie konnte jedoch häufig keine stabile Remission der Augenbeteiligung erreicht werden und die Prognose der Behçet-Uveitis, insbesondere bei Vorliegen einer okklusiven retinalen Vaskulitis, galt lange Zeit als äußerst schlecht. In den letzten Jahren hat die Einführung der Biologika die Therapie des Behçet-Syndroms revolutioniert und die Visusprognose der Patienten deutlich verbessert.

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluate...

Purpose: To assess the efficacy and safety of systemic interferon alpha-2a (IFN) for refractory pseudophakic cystoid macular edema (PCME).Methods: Retrospective observational study. The primary outcome was the decrease of central retinal thickness (CRT). Secondary endpoints were the improvement of best-corrected visual acuity (BCVA) and the assessment of IFN-related side effects.Results: Twenty-four eyes of 20 patients were included. The median CRT was 513 µm (range 220-980 µm) at baseline and decreased to 190 µm (range 140-520 µm) at the last follow-up visit (p < 0.001). Reduction of CRT greater than 100 µm was observed in 22 eyes (92%). The median BCVA (logMAR) increased statistically significant from 0.5 (range 0.2-1.5) at baseline to 0.3 (0-0.8) at the last follow-up (p < 0.001). The BCVA improved in 18 eyes (75%) and remained stable in five eyes (21%). No severe treatment-related side effects occurred.Conclusion: IFN is a very effective agent for treatment of refractory PCME.

ZusammenfassungTopische Kortikosteroide sind effektive entzündungshemmende Medikamente in der Therapie der anterioren Uveitis. Die intraokulare Effektivität der topischen Steroide ist überwiegend durch ihre Penetrationsfähigkeit ins Auge limitiert. Lipophile Präparate wie Dexamethason oder Prednisolonacetat penetrieren besser in die Vorderkammer als hydrophile. Prednisolonacetat 1% ist das Mittel der Wahl in der Behandlung von Patienten mit anteriorer Uveitis. Loteprednol und Fluorometholon besitzen eine schwächere antientzündliche Wirkung, beeinflussen aber weniger den Augeninnendruck und sind deswegen hilfreich bei Patienten mit Steroidresponse. Die antientzündliche Therapie mit lokalen Steroiden muss individuell angepasst werden in Abhängigkeit von Verlauf und Schweregrad der Uveitis. Die häufigsten unerwünschten Wirkungen der lokalen Kortisontherapie sind das steroidinduzierte Glaukom und die Katarakt. Nicht steroidale Antiphlogistika hemmen das Enzym Zyklooxygenase, das für die Bildung proinflammatorischer Prostaglandine zuständig ist. Sie haben eine ergänzende Rolle bei der Behandlung und Vorbeugung postoperativer Reizzustände nach Kataraktoperation. Eine therapeutische Rolle in der Behandlung der Uveitis und des zystoiden Makulaödems sekundär nach Uveitis konnte bisher nicht etabliert werden.

Background/aimsTo evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU).MethodsOpen-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group.ResultsForty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes.ConclusionEC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU.Trial registration numberEUDRACT number: 2009-009998-10, Results.

Purpose: To analyze the efficacy of tocilizumab in uveitic macular edema (ME) resistant to various immunomodulatory drugs.Methods: Patients received tocilizumab every 4 weeks intravenously. Central foveal thickness (CFT) was assessed by optical coherence tomography (OCT).Results: Five patients (8 eyes) who were ineffectively pretreated with systemic prednisolone, at least one immunosuppressive drug, and at least one biologic drug for uveitic macular edema were included in the study. At 3 months, a response of ME (≥25% reduction in CFT) was observed in 6 eyes (75.0%) of 5 patients. During follow-up, complete resolution of ME was achieved in 5 eyes (62.5%) of 4 patients. Improvement of BCVA was observed in 3 eyes of 3 patients, and stabilization in 3 eyes of 3 patients. Tocilizumab was well tolerated, and no severe side effects occurred.Conclusions: Treatment with tocilizumab can be considered in chronic uveitic macular edema even if previous immunomodulatory therapy has failed.

Aim To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Methods Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. Results From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Conclusion Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis.

To present the long-term results of ab externo trabeculotomy in the management of glaucoma secondary to chronic uveitis. In this retrospective single-centre case series, medical records of patients with glaucoma secondary to chronic uveitis, who underwent ab externo trabeculotomy, were evaluated. Two definitions of success were used: intraocular pressure (IOP) 6 ≤ IOP ≤ 21 mmHg (success 1) or 6 ≤ IOP ≤ 21 mmHg and at least 25 % reduction from baseline (success 2). Success was complete when no additional medication was required or qualified when additional medication or cycloablative procedures were required to achieve the specific IOP definition. Twenty-two eyes of 18 patients were included. After 3 years, median IOP decreased from 27 mmHg [range 17–43 mmHg, mean 27.5 mmHg, 95 % confidence interval of the mean (CI) 24.5–30.5 mmHg] to 15 mmHg (range 9–19 mmHg, mean 14.5 mmHg, CI 13–16.1 mmHg). Complete and qualified success 1 was 23 and 45 % after 3 years, respectively. For success 2, the rates were 23 and 32 %, respectively. Hyphema was the most common complication, which resolved completely within 1 month after surgery without further intervention. Trabeculotomy ab externo was moderately successful in glaucoma secondary to chronic uveitis after 3 years. No sight-threatening complications were observed during the follow-up period.

Das choroidale Lymphom ist eine seltene Erkrankung und wird in ein primares und ein sekundares choroidales Lymphom eingeteilt. Das primare choroidale Lymphom gehort zur Gruppe der niedrigmalignen extranodalen Marginalzonen-B-Zell-Lymphome. Die sekundaren choroidalen Lymphome stellen okulare Manifestationen disseminierter systemischer Lymphome dar. Typische klinische Zeichen eines Aderhautlymphoms sind multifokale, gelb-weisliche choroidale Infiltrate. Der Glaskorper ist meistens zellfrei. Das choroidale Lymphom hat eine Tendenz zu transskleralem Wachstum. Im Gegensatz zum primaren choroidalen Lymphom, das haufig einseitig auftritt, ohne Beteiligung der vorderen Augenabschnitte verlauft und eine langsame Progression aufweist, ist das sekundare choroidale Lymphom haufig beidseitig, zeigt eine schnelle Progression mit Beteiligung der vorderen Augenabschnitte sowie mit Glaskorperinfiltration und zahlt zu den hochmalignen Lymphomen. Die endgultige Diagnose eines choroidalen Lymphoms ist nur durch eine histopathologische Untersuchung einer Gewebebiopsie moglich. Die Aderhautbiopsie ist der Goldstandard in der Diagnostik des Aderhautlymphoms. Bis zum jetzigen Zeitpunkt gibt es keinen Algorithmus zur Therapie der choroidalen Lymphome. Die Therapieoptionen beinhalten eine perkutane Strahlentherapie, eine Immuntherapie mit Rituximab und eine Chemotherapie. Die Langzeitprognose beim primaren Aderhautlymphom ist in der Regel gut. Die Prognose bei den sekundaren choroidalen Lymphomen ist von dem Malignitatsgrad des systemischen Lymphoms abhangig.

Purpose The aim of this study was to determine the efficacy of once-daily systemic treatment of ocular rosacea with a slow-release form of 40 mg of doxycycline. Methods Fifteen patients with ocular rosacea were enrolled between February 2010 and October 2012 in a retrospective observational case series. Patient complaints and clinical findings including blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, and fluorescein staining of the cornea were evaluated. The ocular manifestations were scored as follows: 0-absent, 1-mild, 2-moderate, and 3-severe. All measurements were repeated at the 6-week follow-up visit. The mean duration of treatment was 8 months (range, 5-12 months), and the mean duration of the follow-up was 9 months (range, 6-17 months). Results At the baseline visit, 73.3% of the patients had severe complaints, and 80% had severe blepharitis despite topical therapy with artificial tears and eyelid hygiene. After 12 weeks of systemic therapy, severe complaints and blepharitis strongly improved and were seen in only 13.3% and 20% of the patients (P = 0.01). Follow-up investigations 6 to 17 months after discontinuation of the treatment showed further significant improvement of complaints (absent or mild in 66.7% and 20% of the patients, respectively) and blepharitis (absent or mild in 26.7% and 60% of the patients, respectively). One patient had a mild stomach ache so that therapy was shortened to 5 months. Conclusions An antiinflammatory dose of slow-release doxycycline 40 mg given daily may be an effective and safe therapy of ocular rosacea.

Glaucoma is one of the sight-threatening complications of Fuchs' uveitis syndrome (FUS) and the most difficult to manage. The goal of this study was to assess the efficacy and safety of cyclophotocoagulation (CPC) in the management of glaucoma secondary to FUS.In a retrospective analysis, the charts of all patients with FUS referred to our clinic from January 2002 to December 2012 were reviewed. In patients with glaucoma or ocular hypertension, controlled eye pressure was defined using two alternative upper limits of 6 ≤ IOP ≤ 21 mmHg and 6 ≤ IOP ≤ 18 mmHg at 1 year follow-up.One hundred and seventy-six patients with FUS were included in this study. Of those, 28 had ocular hypertension (OHT) or glaucoma. Mean maximal intraocular pressure (IOP) of patients with glaucoma/OHT was 40.8 mmHg. Twenty-three patients (82.1 %) had maximal IOP levels of 35 mmHg or higher. Sixteen patients with glaucoma/OHT underwent CPC alone (ten patients) or in combination with other surgical procedures (six patients). After 1 year, control of IOP for both upper limits (6 ≤ IOP ≤ 18 mmHg) and (6 ≤ IOP ≤ 21 mmHg) was achieved in six of ten patients (60 %) who received CPC alone, and in five of six patients (83.3 %) who required additional surgery after CPC. The mean number of cycloablative procedures was 1.3 (range 1-2) in the CPC alone group and 1.2 (range 1-2) in patients for whom CPC was used as adjunct therapy. There was no exacerbation of intraocular inflammation, no postoperative hypotony and no phthisis bulbi in the 16 patients who underwent CPC.CPC is a safe and effective procedure that should be considered if medical treatment has failed to control glaucoma in FUS.

Purpose: To evaluate the response to treatment in patients with tubulointerstitial nephritis and uveitis (TINU) syndrome over a long-term follow-up period.Methods: Nine patients with TINU syndrome were retrospectively reviewed. The mean follow-up was 54.8 months (range: 24–133 months).Results: The mean number of recurrences per year declined from 1.7 in the 1st year to 0.66 in the 2nd year of treatment. The ocular inflammation responded to local corticosteroids in two patients, systemic corticosteroids in two patients, immunosuppressive therapy in four patients, and anti-TNF-α blocking agent in one patient. The therapy could be discontinued in six (67%) patients after a mean treatment period of 29.5 months. In five patients, remission with the recurrence-free period of 12.8 months was achieved.Conclusions: TINU syndrome was characterized by limited responsiveness to corticosteroid therapy and less by severe complications. A long-term course of immunosuppressants or biologics was necessary to contr...

Objective.Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in theNLRP3gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms.Methods.In a retrospective observational cohort study, consecutive family members were screened for the presence of theNLRP3mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined.Results.Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of theNLRP3gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients.Conclusion.TheNLRP3mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.

To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE).Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center.Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 µg/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes).EFE can be easily confirmed using primary 23-G vitrectomy.

Biologicals are substances produced from living organisms such as recombinant proteins or antibodies, which target cytokines or cell surface receptors resulting in suppression of specific immune effectors potentially leading to ocular inflammatory diseases [45]. There are different classes of biologic agents, including anti-TNF agents, interferon, anti-IL agents, anti B-cell agents, and agents against specific cell surface antigens. All of these biologicals are used off-label in the treatment of ocular diseases. However, indications for considering treatment with biologic agents are primary inflammatory eye diseases refractory to corticosteroids and conventional immunosuppressive drugs. This chapter will bring an update for knowledge about the use of the biologic agents in the treatment of uveitis.

Hintergrund Das Risiko, an einem Glaukom zu erkranken, ist bei schwarzafrikanischen Patienten um das 4- bis 5-Fache erhoht. Einfache und effektive Augeninnendruckmessmethoden sind v. a. in Entwicklungslandern erforderlich.

Die Uveitis bei Morbus Behcet zahlt zu den intraokularen Entzundungen mit schlechter Visusprognose. Auch eine fruhe Therapie mit Kortikosteroiden und Immunsuppressiva konnte eine Erblindung der Patienten haufig nicht verhindern. Mit den sog. Biologika stehen uns heute glucklicherweise hoch wirksame Substanzen zur Verfugung, mit denen rasch Reizfreiheit erzielt sowie weitere Rezidive effektiv vermieden werden konnen. Kurzlich formulierte eine interdisziplinare Expertengruppe im Auftrag der EULAR 9 Empfehlungen zur Therapie des Morbus Behcet, von denen 2 die Augenbeteiligung betreffen. Interferon-α besitzt gegenuber den TNF-α-Antagonisten den Vorteil, dass auch nach Beendigung der Therapie ein hoher Prozentsatz der Patienten langfristig in Remission verbleibt. In unserem Beitrag mochten wir einen aktuellen Uberblick uber die medikamentose Therapie des okularen Morbus Behcet geben.

Dyes such as brilliant blue (BBG) are used during vitreoretinal surgery to visualize anatomical structures. By adding deuterium oxide (D2O), surgeons have tried to create a dye mixture heavier than water to facilitate staining of the inner limiting membrane (ILM) without prior fluid–air exchange. This study investigated the effect of 0.4 ml BBG (Fluoron, Ulm, Germany) mixed with 0.13 ml/ml D2O and D2O on retinal function of a pseudo in vivo model using bovine and human whole mount cultures. Bovine and human retinas were superfused, and the electroretinogram (ERG) was recorded. BBG with 0.13 ml/ml D2O and D2O were applied epiretinally, different staining periods (10, 30, 60 and 120 s) were tested, and ERG recovery was monitored. 1 mM aspartate was added to the nutrient solution to examine the photoreceptor reaction. Reductions of the a- and b-wave amplitudes were found directly after exposure with BBG with 0.13 ml/ml D2O and with D2O in all test series. These effects on the electroretinogram were rapidly and completely reversible within the recovery time for all exposure times. ERG amplitudes measured after dye application at the end of the washout did not differ significantly from those recorded before staining. The clinically used mixture of BBG/D2O seems to be safe for clinical use. Staining periods of more than 120 seconds were not tested.

Purpose: To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in the therapy of ocular mucous membrane pemphigoid (OcMMP).Methods: Ten patients (19 eyes) with OcMMP treated with MMF, who had a follow-up of at least 4 years, were retrospectively analyzed. Main outcome measures were inflammatory control, progression of cicatrization, and side effects.Results: Control of inflammation was achieved in 11 eyes (58%) of 6 patients (rate: 0.11/PY). Mild inflammatory activity was observed in 8 eyes (42%) of 4 patients (rate: 0.07/PY). Progression of conjunctival cicatrization was prevented in 47% (9/19) of the eyes. Mild progression of cicatrization was found in 42% (8/19) of the eyes. Conjunctival cicatrization had progressed to stage IV in 1 patient (11%). Treatment-related side effects occurred in 7 patients (rate: 0.12/PY).Conclusion: MMF is an effective agent for treatment of OcMMP. However, the drug cannot always prevent disease progression.

A high incidence of autoantibodies to lens proteins has been found in sera of patients with uveitis. We showed previously that the anti-lens antibodies reacted predominantly with α-crystallins. The aim of the present study was to identify immunodominant epitopes within the protein chains of human αA- and αB-crystallin. Epitope specificities of antibodies to αA- and αB-crystallin were examined by ELISA using synthetic overlapping peptides, spanning the entire length of both α-crystallins. The peptides consisted of 25 amino acid residues, with an overlap of at least eight amino acids each. The synthetic peptides were tested against sera of 110 patients with different uveitis forms, classified according to anatomical location of intraocular inflammation. Four immunodominant regions within the protein chains of αA- and αB-crystallin could be identified. These regions were recognized by antibodies in sera of 56% of uveitis patients. Anti-lens antibodies of IgG-type reacted preferentially with regions located at amino acid (aa) residues aa:69–93 and aa:137–161 of αA-crystallin as well as aa:69–110 and aa:137–161 of αB-crystallin. IgM antibodies recognized predominantly region aa:149–173 of αA-crystallin, and aa:69–110 and aa:151–175 of αB-crystallin. IgM antibodies directed to peptide aa:69–93 of αB-crystallin were found in sera of 30% of patients with intermediate uveitis. Four immunodominant B-cell epitopes within the protein chains of αA- and αB-crystallin have been identified; however, no clear correlation with the anatomically defined uveitis subtypes has been found except for intermediate uveitis. Whether there may be a correlation with uveitis forms with similar etiopathogenesis has to be evaluated in further studies.

Interferon alpha (IFN-α) and interferon beta (IFN-β) are naturally occurring cytokines, which belong to the type I interferons and share the same receptor leading to very similar therapeutic effects. The immunomodulatory effect of type I interferons includes modulation of antibody production, inhibition of lymphocyte proliferation, inhibition of delayed-type hypersensitivity and enhancement of T-cell and NK-cell cytotoxicity. An increasing number of open clinical studies and case reports have demonstrated the efficacy of IFN-α for severe ocular inflammation in patients with Behcet's disease and of interferon-β, which has been used mainly for the treatment of multiple sclerosis.

Background Detection of tuberculosis as the underlying disease in uveitis can be problematic because of the limited sensitivity of conventional diagnostic methods, especially in the case of latent infection. The aim of our study was to evaluate the clinical usefulness of 18 F-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG-PET/CT) in patients with uveitis and positive interferon-γ release assay. Methods We screened 95 patients with different uveitis forms by QuantiFERON TB-Gold test. Positive results were found in 24 cases. 18 F-FDG-PET/CT was performed in 20 QuantiFERON-positive patients. PET/CT images were evaluated for the presence, size and metabolic activity of hilar and mediastinal lymph nodes and pulmonary lesions. Results In nine patients (45%) PET/CT detected increased FDG uptake in mediastinal or hilar lymph nodes. In two patients Mycobacterium tuberculosis was detected in culture after PET/CT-guided lymph node biopsy. In seven patients (35%) with serpiginous choroiditis partly calcified lymph nodes without FDG-uptake were found. Remission of uveitis was achieved in nine of 11 (82%) anti-tuberculosis-treated patients with progressive course of uveitis. Conclusion In QuantiFERON-positive patients with severe uveitis forms, such as serpiginous choroiditis and occlusive retinal vasculitis, 18 F-FDG-PET/CT is useful to identify lesions appropriate for biopsy and helps to establish the diagnosis and appropriate therapy for presumed tuberculosis-induced intraocular inflammation.

Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

Background: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that effectively controls the intraocular inflammation in adults. Purpose: To assess the efficacy of MMF in uveitis in children and to analyse the possible side effects. Participants and methods: A retrospective analysis was carried out on 17 children (32 eyes) with intraocular inflammation treated with MMF and followed up at the University Eye Hospital Tuebingen, Tuebingen, Germany, between 2000 and 2005. All children had chronic non-infectious uveitis and received MMF for at least 6 months. All patients were given steroids or other immunosuppressive agents before initiating treatment with MMF. Results: 17 children (10 boys and 7 girls) with a mean age of 8 (range 2–13) years at the onset of uveitis were examined. The average duration of follow-up after initiation of MMF was 3 (range 2–5) years. A steroid-sparing effect was achieved in 88% of the patients. The oral prednisolone was successfully discontinued in 41% children and reduced to a daily dose of ⩽5 mg in 47% of the children. 24% of the patients remained relapse-free during the treatment, but a reduction in the relapse rate was observed in all other patients except one. Visual acuity was increased or maintained in 13 children (76%). Mild side effects (headache, rash, gastrointestinal discomfort) occurred in 7 patients (41%) and were the cause of discontinuation of MMF in 1 patient. Conclusion: The results of our study are encouraging and suggest that MMF is an effective agent also in the treatment for uveitis in children, with marked steroid-sparing potential and an acceptable side effect profile.

Purpose: Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not respond sufficiently and there is a high risk of them becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (Humira®), a complete humanised anti-TNF alpha antibody. Methods: We retrospectively analysed 18 patients, who were treated with Adalimumab (20–40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, one was without detectable underlying disease. The age at onset of arthritis varied from 0.5–15 years and for uveitis from 2–19 years. Patients were included when the previous anti-inflammatory therapy had been ineffective. It consisted of systemic steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n = 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n = 3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a) effective: no relapse or more than two relapses less than before treatment, (b) mild: one relapse less than before treatment, (c) no response: no change in relapse rate and (d) worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings), using three out of six parameters of the ACR PED Criteria, was: effective, mild, no response, worsening. Results: For arthritis (n = 16) the response to Adalimumab was effective in 10 of 16 patients, mild in three patients, three did not respond. For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in one child. Additional immunosuppressive treatment was used in seven of the effectively treated children. Due to elevation of liver enzymes in one patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported. Conclusions: For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, were not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear.

Uveitis is an intraocular inflammatory disease in which autoimmune reactions have been discussed in playing an important role. Many data in this respect derived from the animal model of "experimental autoimmune uveitis", where several organ-specific autoantigens have been described such as the retinal S-antigen and the interphotoreceptor retinoid-binding protein. However, their diagnostic and pathogenic role in humans has been controversially discussed. In recent studies, the possible relevance of betaB1-crystallin, present in lens and ciliary body, has been outlined. We, therefore, wanted to analyse whether sera from patients with uveitis might contain antibodies to lens proteinsHuman lenses from cadaveric eyes were shock frozen, homogenized, and resuspended. The resulting suspension (human lens protein fraction--HLPF) was analyzed for antigenicity by ELISA and Western blotting with patients' sera. A total of 165 patients with uveitis, 54 patients with scleritis and episcleritis, 56 patients with other eye diseases, and 112 healthy blood donors were studied.Twenty-six (49%) of the 53 patients with anterior uveitis, 17 (32%) of the 53 patients with intermediate uveitis and 7 (22%) of 32 patients with posterior uveitis reacted in the ELISA with the HLPF. Antibodies to lens antigens were detected in one-third of patients with panuveitis and retinal vasculitis. In contrast, only 12% of the healthy blood donors were positive in the ELISA. The number of patients with an autoimmune response to alpha-crystallins in Western blot predominated in all investigated groups.These data indicate that antibodies to lens proteins occur in a high incidence in sera from patients with uveitis. Forty-nine percent of the patients with anterior uveitis and only 12% of healthy controls were positive in the ELISA. In our groups of patients and controls the autoantibodies reacted in the Western blot predominantly with alpha-crystallin. Further studies are required to analyze in more detail the clinical and etiopathogenetic relevance of the antilens antibodies in uveitis.

Aim: To assess the long-term efficacy and tolerability of both derivatives of mycophenolic acid, mycophenolate mofetil (MMF) and mycophenolate sodium (MPS), in the therapy of patients with birdshot chorioretinopathy (BSCR). Methods: Retrospective analysis of 24 patients (48 eyes) with BSCR, treated with MMF or MPS with a follow-up of at least 1 year. The main outcome measures included control of inflammation, steroid-sparing potential and side effects. Secondary outcome measure was the development of retinal function during the therapy measured by best-corrected visual acuity (BCVA), visual field and/or electroretinography (ERG). Results: Twelve patients (50%) were treated with MMF and 12 patients (50%) with MPS. Control of intraocular inflammation, defined as complete lack of clinical and angiographic signs of inflammatory activity, was achieved in 16 of 24 patients (67%). The angiographic signs of activity were significantly reduced during the follow-up (p0.05). In 20 out of 21 patients (95%) who received systemic corticosteroids, the corticosteroids could be tapered to a daily dose of ≤10 mg (rate 0.26/patient-year). Drug-related side effects occurred in 12 patients (50%, rate 0.16/patient-year). In four patients (17%), a therapy switch from MMF to MPS was undertaken due to gastrointestinal discomfort. Conclusions: Derivatives of mycophenolic acid are effective and safe drugs for the treatment of BSCR. In cases with gastrointestinal side effects, a therapy switch from MMF to MPS should be considered.

Aim The aim of the study was to assess the long-term efficacy and tolerability of tumour necrosis factor α (TNFα) inhibitors in the therapy of children with refractory antinuclear antibody (ANA)-associated chronic anterior uveitis. Methods Retrospective analysis of 31 children with ANA-associated uveitis, treated with TNFα inhibitors with a follow-up period of at least 2 years. The outcome measures included: control of inflammation, corticosteroid-sparing potential and side effects. Results Twenty-three children (74%) were treated with adalimumab, five children (16%) with infliximab and three children (10%) with etanercept. Control of uveitis, defined as 0 anterior chamber cells while on ≤2 drops/day topical corticosteroids, was achieved in 22 of 31 patients (71%) after 1 year (95% CI 52% to 86%), and in 21 of 29 patients (72%) after 2 years of treatment (95% CI 53% to 87%). Control of uveitis was observed in 18 of 23 children (78%) treated with adalimumab, and in two of five children (40%) treated with infliximab. In all children treated with etanercept, no sufficient inflammatory control was found. Systemic corticosteroids could be discontinued in 71% (12/17 children) and topical corticosteroids in 55% (17/31) of the patients. Treatment-related side effects were found in nine children (29%, rate: 0.10/patient-year). Conclusions Our data show that adalimumab and infliximab have beneficial effects in the therapy of severe ANA-associated anterior uveitis in children.

Purpose: To report on the occurrence of tubulointerstitial nephritis and uveitis (TINU) and HLA typing in two siblings.Design: Retrospective case study.Methods: HLA typing from two siblings with TINU syndrome and their parents was performed on DNA from peripheral blood mononuclear cells (PBMC).Results: The boy developed TINU syndrome in 2001, his sister 5 years later. Both siblings inherited the HLA alleles HLA-DRB1*1401 and HLA-DQB1*0503 on the maternal haplotype, a haplotype that had rarely been observed in patients with TINU.Conclusions: The observations support inheritance of HLA-linked risk factors of TINU, but indicate heterogeneity of the risk phenotype due to linkage with different reported haplotypes.

To assess the short-term and long-term efficacy of oral therapy with valganciclovir in patients with Posner-Schlossman Syndrome (PSS). This is a retrospective observational study on 11 patients with PSS treated with valganciclovir. The PSS was diagnosed clinically on the basis of recurrent episodes of anterior uveitis associated with attacks of elevated intraocular pressure (IOP). All patients who did not respond to aciclovir, or whose cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) analysis of the aqueous humour was positive, were treated with valganciclovir (Valcyte®). Initially, the drug was given 900 mg twice daily for 3 weeks, followed by 450 mg twice daily for a mean period of 20 months (range 10–46 months). Eleven patients with mean age of 44 years were included in this study. Four of 11 patients were working in a sanitary profession. Before initiation of valgancicloivir therapy, the highest IOP was 68 mmHg (mean 45 mmHg ±9 mmHg). In the first week of treatment, the IOP decreased significantly (mean 16 mmHg ±10 mmHg) and maintained stability during the entire treatment period. In seven of 11 (63.6 %) patients, valganciclovir led to resolution of inflammatory activity and stable IOP. In six patients, the therapy could be discontinued after a mean of 14 months. However, two patients had a recurrence after discontinuation of valganciclovir treatment. No side effects of therapy were observed. Long-term oral therapy with valganciclovir seems to lower the recurrence rate in patients with clinically diagnosed PSS.

The effects of a glutathione-containing intraocular irrigation solution, BSS Plus®, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD] = 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity.

Purpose: To describe treatment of chronic Irvine-Gass syndrome (CME) with interferon (IFN) alpha.Methods: Interventional retrospective case series. IFN alpha-2a was administered at a dose of 3 million IU/day subcutaneously for 4 weeks, and was tapered thereafter. Treatment efficacy was assessed by best-corrected visual acuity (BCVA) and by optical coherence tomography (OCT).Results: Three patients (4 eyes) with chronic Irvine-Gass syndrome were treated. Ineffective pretreatment included local and systemic corticosteroids. Within 4 weeks, IFN alpha led to resolution of CME in all eyes. BCVA improved in 3 eyes and remained unchanged in 1 eye. During follow-up of 3–11 months no relapse of CME occurred. No systemic or local side effects were noted.Conclusions: IFN alpha has been demonstrated to be a successful and well-tolerated treatment option for resistant chronic pseudophakic CME. Further studies are necessary to evaluate the role of IFN alpha in Irvine-Gass syndrome.

Ziele: Die Diagnostik der Tuberkulose (Tb)-induzierten Uveitis stellt eine diagnostische Herausforderung dar, insbesondere bei Fehlen direkter Hinweise auf eine aktive Tb-Infektion. Wir untersuchten, ob die 18F-FDG-PET/CT fur die Diagnose der Tb bei Patienten mit Uveitis und positivem QuantiFERON-TB Test sowie negativer Vordiagnostik einen Nutzen bietet. Methode: Bei 20 QuantiFERON+ Patienten mit Uveitis wurde ein PET/CT mit 350 MBq 18F-FDG und kontrastangehobener CT durchgefuhrt. Vor der PET/CT durchliefen alle Patienten eine umfassende klinische Diagnostik, inklusive Rontgen u/o CT des Thorax. Die PET/CT-Scans wurden hinsichtlich Nachweis, Grose und metabolischer Aktivitat(SUVmax) hilarer und mediastinaler LK sowie pulmonaler Lasionen ausgewertet. Es wurden auch LK

Short-term studies have shown mycophenolate mofetil (MMF) to be a useful immunosuppressive agent for the treatment of intraocular inflammation. The aim of our study was to assess the long-term efficacy and tolerability of MMF in patients with chronic non-infectious uveitis, as well as to analyze disease course following discontinuation of therapy. This is a retrospective case series on 60 uveitis patients treated with MMF with a follow-up period of at least 5 years. The main outcome measures were: control of inflammation, corticosteroid-sparing potential, side-effects, ability to stop/taper MMF treatment because of effective control of inflammation and relapse rate after therapy discontinuation. Control of intraocular inflammation (efficacy of MMF), defined as inactive disease under prednisolone dose of ≤10 mg daily, was achieved in 43 of 60 patients (72%) after 1 year of MMF treatment at a rate of 0.72 per patient-year (PY), and in 45 of 55 patients (82%) after 2 years therapy (rate: 0.41/PY). An improvement (3 lines) or stabilization of visual acuity was observed in 49 patients (82%), and a worsening in 11 patients (18%, 95% CI: 10–30%). The probability of discontinuing prednisolone, estimated by the Kaplan–Meier method, was 40% after 5 years therapy. The probability of discontinuing mycophenolate mofetil due to efficacy was 33% after 5 years treatment. Recurrences of uveitis occurred in six of 21 patients (29%, rate: 0.11/PY) after MMF discontinuation due to efficacy. The treatment was stopped because of inefficacy in 12 patients (rate: 0.05/PY) and because of side-effects in four patients (rate: 0.02/PY). The rate of adverse effects during MMF therapy was 0.17/PY. Our data show that mycophenolate mofetil is generally effective and well tolerated in the treatment of chronic non-infectious uveitis.

The diagnosis of tuberculosis as an etiological factor in patients with uveitis is difficult because of lack of specific diagnostic tests. The authors report 2 cases of occlusive retinal vasculitis, in which (18)F-FDG-PET/CT was helpful for the diagnosis of tuberculosis as a presumptive cause of intraocular inflammation.In 2 patients with severe occlusive retinal vasculitis and positive QuantiFERON TB-Gold test, (18)F-FDG-PET/CT, transbronchial needle-aspiration biopsy, and microbiological investigation were performed.(18)F-FDG-PET/CT showed increased fluorodeoxyglucose uptake in some mediastinal and hilar lymph nodes. After needle-aspiration biopsy of PET-positive lymph nodes, M. tuberculosis was recovered in culture in both cases. Remission of uveitis was achieved only after a combination therapy with 3 anti-tubercular agents and systemic steroids.The authors favor the use of (18)F-FDG-PET/CT in patients with sight-threatening intraocular inflammation and positive interferon-gamma release assay. Anti-tubercular therapy, together with anti-inflammatory treatment, may lead to a remission in such patients.

Purpose: To assess the efficacy and tolerability of mycophenolate sodium (MPS) in patients with uveitis.Methods: Retrospective analysis including uveitis patients treated with MPS (Myfortic®) for at least 3 months duration. MPS was administered in a dose of 720 mg twice daily.Results: We analyzed 35 patients (65 affected eyes) with anterior (n = 5), intermediate (n = 23), posterior (n = 6), and panuveitis (n = 1). Previous treatment consisted of systemic corticosteroids in all patients and at least one immunomodulating agent in 15 patients. Mean duration of MPS therapy was calculated as 9.6 months (3–31 months). MPS was able to control intraocular inflammation without relapse in 30 patients (85.7%). Stabilization or improvement of visual acuity was achieved in 60 eyes (92.3%). Tolerability of MPS was good or moderate in 34 patients (97.1%).Conclusions: MPS was demonstrated as an effective and well-tolerated immunosuppressive drug for different forms of uveitis.

Aim: To assess the efficacy and tolerability of interferon (IFN) alpha in chronic cystoid macular oedema (CMO) due to non-infectious uveitis. Methods: Retrospective analysis of an interventional case series. IFN alpha-2a was administered at an initial dose of 3 or 6 million IU per day subcutaneously and tapered afterwards to the lowest possible dose to maintain the absence of CMO. Treatment efficacy was assessed by optical coherence tomography. Results: Twenty-four patients with chronic CMO (median duration 36.0 months) due to non-infectious anterior (n = 2), intermediate (n = 18) or posterior (n = 4) uveitis have been analysed. Ineffective pretreatment included systemic corticosteroids (all patients), acetazolamide (22 patients) and at least one immunosuppressive drug (18 patients). IFN therapy was shown to be effective ( = complete resolution of CMO within 3 months, able to taper IFN) in 15 patients (62.5%), partly effective ( = incomplete resolution of CMO, unable to taper IFN) in six patients (25.0%) and not effective ( = no response or recurrence of CMO) in three patients (12.5%). IFN treatment was generally well tolerated. Common side effects including flu-like symptoms, fatigue or increased liver enzymes were dose-dependent and led to discontinuation of IFN in only one patient. Conclusion: The data demonstrate IFN alpha to be an effective and well-tolerated therapy for chronic refractory uveitic CMO.