Biologics in the Treatment of Uveitis. / Therapie der Uveitis mit Biologika.

GOAL: To provide an overview of biologics that are used to treat noninfectious uveitis, including their different targets, modes of actions, and indications. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Drug-induced Sarcoid Uveitis with Biologics.

PURPOSE/OBJECTIVES: to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Biologic treatment-induced uveitis often presents as granulomatous disease.

Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea.

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 evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.

[Uveitis in Behçet's Syndrome in Germany - Prognosis During Current Therapy]. / Uveitis bei Behçet-Syndrom in Deutschland ­ Prognose unter aktueller Therapie.

Behçet's syndrome (BS) is an inflammatory systemic disease associated with multiple organ manifestations. Major symptoms include oral and genital ulcerations, skin lesions and uveitis. Diagnosis of Behçet's syndrome is based on clinical findings. A typical for ocular Behçet's syndrome is recurrent non-granulomatous panuveitis with occlusive retinal vasculitis. Treatment used to be based only on the use of systemic corticosteroids and conventional immunosuppressives, but most often this treatment did not appear to be sufficient. In consequence, prognosis of ocular BS was very poor over a long period of time - especially if occlusive retinal vasculitis was present. In recent years, the introduction of biologicals has revolutionised the therapeutic regime and consecutively visual prognosis of ocular Behçet's syndrome has dramatically improved.

Interferon Alpha for Refractory Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome).

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.

[Topical Corticosteroids and Non-steroidal Anti-inflammatory Drugs in the Therapy of Non-infectious Uveitis]. / Topische Kortikosteroide und nicht steroidale Antiphlogistika zur Behandlung der nicht infektiösen Uveitis.

Topical corticosteroids are effective anti-inflammatory drugs in the treatment of anterior uveitis. The intraocular efficacy of topical corticosteroids mostly depends on their intraocular permeability through the cornea. Lipophile derivatives such as dexamethasone and prednisolone acetate penetrate better into the anterior chamber than hydrophilic derivatives. Prednisolone acetate 1% is the first choice in the therapy of patients with anterior uveitis. Loteprednole and fluorometholone have a slightly weaker anti-inflammatory effect, but they induce less elevation of intraocular pressure and might be helpful in the treatment of patients with steroid response. Topical corticosteroid therapy has to be individually adapted, depending on the clinical course and severity of uveitis. The most common side effects of topical corticosteroids are corticosteroid-induced glaucoma and corticosteroid-induced cataracts. Non-steroidal anti-inflammatory drugs inhibit the enzyme cyclooxygenase that is responsible for the formation of pro-inflammatory prostaglandins. These have an adjunctive role in the treatment and prevention of post-operative inflammation after cataract surgery. A therapeutic role of topical NSAID to treat uveitis and cystoid macular oedema secondary to uveitis has not yet been established.

Long-term Follow-up of Patients with Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome.

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 control the uveitis and led to induction of remission.

Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial.

BACKGROUND/AIMS: To 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). METHODS: Open-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. RESULTS: Forty-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. CONCLUSION: EC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU. TRIAL REGISTRATION NUMBER: EUDRACT number: 2009-009998-10, Results.

Outcomes of Primary Transconjunctival 23-Gauge Vitrectomy in the Diagnosis and Treatment of Presumed Endogenous Fungal Endophthalmitis.

PURPOSE: To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE). METHODS: Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center. RESULTS: 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). CONCLUSIONS: EFE can be easily confirmed using primary 23-G vitrectomy.

Outcomes of Ahmed Glaucoma Valve Implantation for Glaucoma Secondary to Fuchs Uveitis Syndrome.

PURPOSE: To present the outcomes of Ahmed glaucoma valve implantation (AGV) in glaucoma secondary to Fuchs uveitis syndrome (FUS). METHODS: In this retrospective chart review, two definitions of success were used: 6 mmHg ≤intraocular pressure (IOP) ≤21 mmHg (success 1), and 6 mmHg ≤ IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). Depending on the need of postoperative antiglaucoma medication, success was defined as either complete or qualified. RESULTS: In total, 17 eyes of 17 patients were included. Complete success rates (both definitions) were 23.5% (n = 17) after 1 year and 23% (n = 13) after 3 years. Qualified success rates (both definitions) were 58.3% (n = 17) after 1 and 38.4% (n = 13) after 3 years. Encapsulated bleb formation was the most common complication (47% of eyes). CONCLUSIONS: AGV was moderately successful in the management of glaucoma secondary to FUS. Success rates are improved by medications, needling, and cycloablative procedures.

Tocilizumab in Uveitic Macular Edema Refractory to Previous Immunomodulatory Treatment.

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.

Comparison of ab externo trabeculotomy in primary open-angle glaucoma and uveitic glaucoma: long-term outcomes.

BACKGROUND: The aim of this study was to compare the long-term outcomes of ab externo trabeculotomy in primary open-angle glaucoma (POAG) and uveitic glaucoma (UG). DESIGN: This was a retrospective single-center case series study. PARTICIPANTS: Twenty eyes of 17 patients with POAG and 22 eyes of 18 patients with UG were included in this study. PATIENTS AND METHODS: The medical records of all consecutive patients with POAG and UG who underwent ab externo trabeculotomy since 2004 were reviewed. MAIN OUTCOME MEASURE: The main outcome measure was change in median intraocular pressure (IOP). Success was defined as IOP ≤21 mmHg (success 1) and IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). RESULTS: In the POAG group, the median IOP decreased significantly from 22 mmHg (95% CI 21-25 mmHg; n=20) at baseline to 14 mmHg (95% CI 12-16; n=13) after 4 years, P<0.001. In the UG group, the median IOP decreased significantly from 27 mmHg (95% CI 24.5-30.5 mmHg; n=22) at baseline to 12 mmHg (95% CI 9-15 mmHg; n=15) after 4 years, P<0.001. Seven eyes in the UG group failed within the first year after surgery compared to none in the POAG group. Of these, four eyes had Fuchs' uveitis syndrome and two had granulomatous uveitis. No sight-threatening complications occurred in both POAG and UG groups. CONCLUSION: Ab externo trabeculotomy effectively reduced IOP in both UG and POAG groups. However, the success rates in the UG group were significantly lower due to the high failure rate in patients with Fuchs' uveitis syndrome and granulomatous uveitis. The procedure demonstrated a high safety profile in both UG and POAG patients.

NLRP3 A439V Mutation in a Large Family with Cryopyrin-associated Periodic Syndrome: Description of Ophthalmologic Symptoms in Correlation with Other Organ Symptoms.

OBJECTIVE: Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1ß. 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 the NLRP3 mutation. 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 the NLRP3 gene 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: The NLRP3 mutation 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.

Long-term results of ab externo trabeculotomy for glaucoma secondary to chronic uveitis.

PURPOSE: To present the long-term results of ab externo trabeculotomy in the management of glaucoma secondary to chronic uveitis. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

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.

Mycophenolic acid in the treatment of birdshot chorioretinopathy: long-term follow-up.

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 (p<0.05). No significant difference was found in the mean BCVA, the visual field and the ERG parameters during the treatment compared with the baseline (p>0.05). 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.

Treatment of ocular rosacea with once-daily low-dose doxycycline.

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.

Is cyclophotocoagulation an option in the management of glaucoma secondary to Fuchs' uveitis syndrome?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: CPC is a safe and effective procedure that should be considered if medical treatment has failed to control glaucoma in FUS.

Immunomodulatory therapy with tumour necrosis factor α inhibitors in children with antinuclear antibody-associated chronic anterior uveitis: long-term results.

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.

Testing the biocompatibility of a glutathione-containing intra-ocular irrigation solution by using an isolated perfused bovine retina organ culture model - an alternative to animal testing.

The effects of a glutathione-containing intra-ocular 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.