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.

[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.

[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 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.

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.

A case of AZOOR under immunomodulatory treatment.

PURPOSE: To describe the clinical course and treatment response of a case of Acute Zonal Occult Outer Retinopathy (AZOOR). METHODS: This is an observational case report. The examinations included ophthalmic examination, longitudinal multimodal imaging, visual field testing, electrophysiological recordings, serologic analyses and whole genome sequencing. RESULTS: In this report, the authors present the case of an otherwise healthy 33-year-old female with bilateral AZOOR manifestation. Other possible causes of the observed retinal lesions were ruled out by extensive diagnostic work-up. Treatment with oral prednisolone therapy led to temporal disease control but progression was observed after prednisolone discontinuation. A tapered oral prednisolone therapy in combination with adalimumab initiation prevented further progression for at least 21 months. CONCLUSION: Diagnosis of AZOOR is frequently complicated by the unspecific symptoms of the disease and significant number of differential diagnoses. Complete diagnostic work-up is important to rule out other etiologies. Due to the lack of randomized controlled trials, therapeutic decisions obligatorily rely on empiric treatment decisions in combination with frequent follow-up examinations.

Identification of immunodominant epitopes of alpha-crystallins recognized by antibodies in sera of patients with uveitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluating retinal toxicity of a new heavy intraocular dye, using a model of perfused and isolated retinal cultures of bovine and human origin.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The clinically used mixture of BBG/D2O seems to be safe for clinical use. Staining periods of more than 120 seconds were not tested.

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.

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.

Long-term results of therapy with mycophenolate mofetil in chronic non-infectious uveitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our data show that mycophenolate mofetil is generally effective and well tolerated in the treatment of chronic non-infectious uveitis.

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.

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.

Interferon-alpha-associated presumed ocular sarcoidosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Adalimumab in the therapy of uveitis in childhood.

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.

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.

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.