Sibylle Winterhalter

Anti-TNF-Therapie bei Uveitis

ZusammenfassungBiologika sind selektiv wirksame Proteine, die biotechnologisch hergestellt werden und in der Behandlung chronischer Erkrankungen einen wesentlichen Fortschritt darstellen. Besondere Bedeutung kommt Biologika zu, die sich gegen das Zytokin Tumor-Nekrose-Faktorxa0α (TNF-α) richten, das eine Schlüsselrolle in der Pathophysiologie chronisch entzündlicher Erkrankungen einnimmt. Experimentelle und klinische Untersuchungen zeigen, dass TNF-α auch bei intraokularen Entzündungen beteiligt ist und die gezielte Blockade von TNF-α ein vielversprechender Ansatz in der Uveitistherapie ist. Diese Übersicht stellt Grundzüge der Wirkung und Anwendung von TNF-Blockern bei der Behandlung intraokularer Entzündungen mit deren besonderen Wirkungen und Nebenwirkungen in diesem Erkrankungsgebiet dar.AbstractBiologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.

[Behçet's disease - ophthalmological and general aspects part I : etiology, pathogenesis and diagnostics].

Behçets disease (also known as morbus Behcet or Admantiades-Behcet syndrome) is a chronic vasculitis mainly characterized by recurrent mucocutaneous lesions and sight threatening uveitis. It may also involve joints, vessels of all sizes and the central nervous system. Because of its severe morbidity and considerable mortality early diagnosis and treatment is important. Treatment and prognosis of this disorder have profited considerably in recent years following the introduction of biologic agents. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the diagnosis and therapy of Behçets disease.ZusammenfassungDas Behçet-Syndrom (auch Morbus Behçet oder Adamantiades-Behçet-Erkrankung) ist eine chronische Vaskulitis, die hauptsächlich durch rekurrierende mukokutane Läsionen und visusbedrohende intraokulare Entzündungen charakterisiert ist. Es kann darüber hinaus Gelenke, alle Gefäßbahnen und das zentrale Nervensystem betreffen. Aufgrund hoher Morbidität und erheblicher Mortalität sind eine frühe Diagnostik und adäquate Therapie von großer Bedeutung. Die Behandlung und Prognose der Erkrankung konnten in den letzten Jahren deutlich durch die Einführung der „Biologika“ profitieren. Dieser Beitrag fasst den aktuellen Wissensstand zusammen und unterstreicht die bedeutende Rolle des Augenarztes bei der Diagnostik des Behçet-Syndroms.AbstractBehçet’s disease (also known as morbus Behcet or Admantiades-Behcet syndrome) is a chronic vasculitis mainly characterized by recurrent mucocutaneous lesions and sight threatening uveitis. It may also involve joints, vessels of all sizes and the central nervous system. Because of its severe morbidity and considerable mortality early diagnosis and treatment is important. Treatment and prognosis of this disorder have profited considerably in recent years following the introduction of biologic agents. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the diagnosis and therapy of Behçet’s disease.

[Behcet's disease--ophthalmological and general aspects: Part 2: Therapy].

ZusammenfassungDas Behçet-Syndrom (auch Morbus Behçet oder Admantiades-Behçet-Erkrankung) ist eine chronische Vaskulitis. Die Erkrankung ist durch Exazerbation und Remission einer Vielzahl von Symptomen und Organmanifestationen charakterisiert. Die Befunde variieren von milden mukokutanen Läsionen bis zu schweren, visusbedrohenden intraokularen Entzündungen. Es kann darüber hinaus Gelenke, alle Gefäßbahnen und das zentrale Nervensystem betreffen. Aufgrund hoher Morbidität und erheblicher Mortalität ist eine adäquate Therapie von großer Bedeutung. Cyclosporinxa0A ist das bisher in Deutschland einzig zugelassene Therapeutikum zur Behandlung der Augenbeteiligung. Neuro- und Nephrotoxizität schränken den Einsatz allerdings ein. Bei Patienten mit schweren Uveitisverläufen haben sich „Biologika“ als therapeutischer „Durchbruch“ erwiesen. Interferon-α hat sich als sehr wirksam bei intraokularer Entzündung gezeigt. Monoklonale Antikörper gegen TNF-α und Interleukin-1 sind ebenfalls in klinischen Studien effektiv gewesen und sind in einigen Ländern für diese Indikation bereits zugelassen. Dieser Beitrag fasst den aktuellen Wissenstand zusammen und unterstreicht die bedeutende Rolle des Augenarztes in der Therapie des Behçet-Syndroms.AbstractBehcet’s disease (also called Admantiades-Behcet syndrome) is a chronic vasculitis. The disease is characterized by exacerbations and remissions of symptoms and organ manifestations and may produce only mild mucocutaneous lesions, whereas ocular lesions can cause blindness. In addition, involvement of the gastrointestinal tract, central nervous system (CNS) and large blood vessels is sometimes life-threatening. Cyclosporin A is the only agent for treatment of ocular lesions registered in Germany; however, the neurotoxicity and nephrotoxicity restrict usage of the drug. In patients suffering from severe uveitis, biologics have been a breakthrough. Interferon (IFN) alpha therapy has shown significant efficacy for intraocular inflammation. Monoclonal antibodies to TNF-alpha and interleukin-1 have been successful in clinical trials and are approved in some countries. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the therapy of Behcet’s disease.Behcets disease (also called Admantiades-Behcet syndrome) is a chronic vasculitis. The disease is characterized by exacerbations and remissions of symptoms and organ manifestations and may produce only mild mucocutaneous lesions, whereas ocular lesions can cause blindness. In addition, involvement of the gastrointestinal tract, central nervous system (CNS) and large blood vessels is sometimes life-threatening. Cyclosporin A is the only agent for treatment of ocular lesions registered in Germany; however, the neurotoxicity and nephrotoxicity restrict usage of the drug. In patients suffering from severe uveitis, biologics have been a breakthrough. Interferon (IFN) alpha therapy has shown significant efficacy for intraocular inflammation. Monoclonal antibodies to TNF-alpha and interleukin-1 have been successful in clinical trials and are approved in some countries. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the therapy of Behcets disease.

[Anti-TNF-α treatment for uveitis. Analysis of the current situation].

ZusammenfassungBiologika sind selektiv wirksame Proteine, die biotechnologisch hergestellt werden und in der Behandlung chronischer Erkrankungen einen wesentlichen Fortschritt darstellen. Besondere Bedeutung kommt Biologika zu, die sich gegen das Zytokin Tumor-Nekrose-Faktorxa0α (TNF-α) richten, das eine Schlüsselrolle in der Pathophysiologie chronisch entzündlicher Erkrankungen einnimmt. Experimentelle und klinische Untersuchungen zeigen, dass TNF-α auch bei intraokularen Entzündungen beteiligt ist und die gezielte Blockade von TNF-α ein vielversprechender Ansatz in der Uveitistherapie ist. Diese Übersicht stellt Grundzüge der Wirkung und Anwendung von TNF-Blockern bei der Behandlung intraokularer Entzündungen mit deren besonderen Wirkungen und Nebenwirkungen in diesem Erkrankungsgebiet dar.AbstractBiologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.

Diagnostics and treatment of primary vitreoretinal lymphoma

ZusammenfassungHintergrundBeim primären vitreoretinalen Lymphom (PVRL), einem seltenen hämatopoetischen okulären Tumor, handelt es sich meist um ein großzelliges diffuses B-Zell-Lymphom. Das PVRL, das früher auch als primäres intraokulares Lymphom (PIOL) bezeichnet wurde, ist eine Unterart des primären ZNS-Lymphoms (PZNSL). DiagnostikDie Diagnose gestaltet sich häufig sehr schwierig, da klinisch eine intermediäre bzw. posteriore Uveitis imitiert wird. Dies wird auch als sog. „Masquerade-Syndrom“ bezeichnet. Notwendig für die endgültige Diagnose sind immunhistochemische, zytologische, pathologische und auch molekularpathologische Untersuchungen der operativ gewonnenen okulären Gewebe. Als hilfreich hat sich auch die Zytokinbestimmung (Interleukin-10) entweder im Vorderkammerpunktat oder im Glaskörpergewebe erwiesen. TherapieLeider zeigen sich die Therapien, die erfolgreich in der Behandlung der systemischen Lymphome sind, weniger effektiv in der Therapie des PVRLs und des PZNSLs. Daher werden heutzutage beim PVRL, zeitweise in Kombination mit einer Radiatio, aggressive chemotherapeutische Substanzen wie Methotrexat und Rituximab appliziert. Hierbei werden beide Chemotherapeutika sowohl systemisch als auch lokal verabreicht. Lediglich beim monokularen PVRL wird die alleinige intravitreale Gabe einer dieser Substanzen diskutiert. Bisher herrscht noch Uneinigkeit, ob die lokale Monotherapie ausreichend ist. Das PVRL reagiert meist sehr gut auf die initiale Therapie, jedoch kommt es im Verlauf häufig zu Rezidiven wie auch zum Auftreten einer ZNS-Manifestation, welche die Prognose quoad vitam deutlich limitieren.AbstractBackgroundPrimary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, mostly a diffuse large B-cell lymphoma. The PVRL, previously called primary intraocular lymphoma (PIOL), is a subset of primary central nervous system lymphoma (PCNSL). DiagnosisThe diagnosis of PVRL is often difficult as it often mimics chronic intermediate or posterior uveitis; therefore, PVRL requires various procedures for the diagnostics, e.g. immunohistochemistry, cytology, pathology, molecular pathology and cytokine analysis (interleukin 10) after surgically obtaining ocular specimens.TherapyTreatment forms that are effective for systemic lymphomas have not been reliably successful for PVRL and PCNSL. Current management of PVRL consists of chemotherapy, such as methotrexate or rituximab, possibly combined with external beam radiation whereby both chemotherapeutic agents are administered systemically as well as intravitreally. Intravitreal treatment alone is recommended solely in the case of monocular PVRL, which is highly controversial. A PVRL usually responds well to initial treatment; however, relapse rates and CNS involvement are high, resulting in a poor prognosis and limited survival.

Optical coherence tomography angiography in comparison with other multimodal imaging techniques in punctate inner choroidopathy

Aims To characterise punctate lesions and choroidal neovascularisation (CNV) in eyes with punctate inner choroidopathy (PIC) using current standard multimodal imaging techniques and optical coherence tomography angiography (OCTA). Methods In our prospective, single-centre study, 20 individuals with PIC underwent imaging with spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), indocyanine green angiography, fundus autofluorescence, fundus colour photography and OCTA. Results Thirty-two eyes of 20 patients were affected. Eight (20%) eyes revealed typical punctate lesions, while 24 (60%) eyes had confirmed CNV on SD-OCT and FA in addition to punctate lesions. Of these 24 eyes with CNV, a reoccurrence of active CNV was detected in 5 (21%) eyes, a residual fluid in 3 (13%) eyes, while 16 (67%) eyes were defined as being stable. On OCTA, CNV was classified as having ‘lacy wheel’, ‘pruned large-trunk’ and ‘dead tree aspect’ vessel shapes with or without areas of non-perfusion. The disease activity was dependent on several predictors in the regression analysis such as intraretinal fluid (p=0.0014), CNV type (p=0.0199), leakage (p<0.0001) and hypoperfusion/non-perfusion (p<0.0001) on OCTA. Conclusion OCTA offers additional valuable insight into the current standard multimodal imaging techniques used for characterisation of PIC. This imaging technique can be a useful tool for analysis of disease activity.

Multimodal Imaging in Birdshot Retinochoroiditis

ABSTRACT Purpose: To describe retinal vascular changes in Birdshot Retinochoroiditis (BSRC) with multimodal imaging techniques and functional values. Methods: In this single-center study, 64 eyes of 32 subjects with BSRC were classified according to disease activity and duration and underwent imaging with spectral domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and optical coherence tomography angiography (OCTA). Results: Mean age of the patients was 60 years (range, 38–74). OCTA revealed capillary loops (58%), telangiectatic vessels (44%), increased intercapillary spaces (52%), altered vascular architecture (53%), and rarefication of C-scans (63%) in retinal layers. Increased rarefications of C-scans (p = 0.0056; p = 0.0046) and altered vascular architecture (p = 0.0120; p = 0.0243) in superficial and deep capillary layers were significantly correlated with disease activity. Conclusion: OCTA adds new insights in a multimodal imaging approach of retinal vascular layer visualization in BSRC and may contribute to existing methods for diagnosing severity and potentially progression of the disease.

Dexamethasone Inserts in Noninfectious Uveitis: A Single-Center Experience

PURPOSEnTo report the effectiveness of repeated intravitreal dexamethasone (DEX) inserts in noninfectious uveitis patients.nnnDESIGNnProspective, single-center, interventional clinical trial between February 2010 and Marchxa02015.nnnPARTICIPANTSnPatients with noninfectious uveitis with cystoid macular edema and/or vitreitis.nnnMETHODSnPatients were treated with a 700-μg intravitreal DEX insert (Ozurdex; Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months after injection. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events were recorded.nnnMAIN OUTCOME MEASURESnPrimary outcome was the reduction of CRT. Secondary outcome was the improvement in BCVA and reduction of VH.nnnRESULTSnIn total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were women (68%). The mean age of all participants was 57 years (range, 24-88 years). More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections were 1.54±0.5 (standard deviation [SD]), 1.98±0.84, and 2.46±1.1 over 12, 18, and 24 months, respectively. Central retinal thickness decreased significantly (P < 0.001) from 465 μm at baseline to 318, 342, and 388 μm after 1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a second, third, and fourth DEX insert. Patients with idiopathic uveitis and sarcoidosis benefited well from DEX inserts. The greatest overall benefit was achieved in patients with no systemic treatment and patients receiving antimetabolites and cyclosporin A. A significant VH score reduction was documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6 months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and after 3 months (Pxa0= 0.001) was seen.nnnCONCLUSIONSnThe repeated longer-term administration of DEX inserts in noninfectious uveitis patients, either alone or in combination with other therapies, led to improved CRT, BCVA, and VH. Underlying diseasesxa0and concomitant systemic therapy seem to have an impact on overall treatment benefit. Ocular complications were reversible and were managed by local treatment, with exception of cataract formation.

Real-life clinical data for dexamethasone and ranibizumab in the treatment of branch or central retinal vein occlusion over a period of six months

PurposeTo evaluate the therapeutic outcome for dexamethasone implant (DEX) or intravitreal ranibizumab (IVR) injections over 6xa0months in patients with macular edema due to branch or central retinal vein occlusion (BRVO, CRVO), in a real-life setting.MethodsA total of 107 patients with BRVO or CRVO were included into this retrospective single-center observational study. Patients were treated with monotherapy consisting of DEX or three monthly IVR injections following a pro re nata regimen (PRN). Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP) were compared between the two therapy groups after 1, 3 and 6xa0months.ResultsBRVO patients treated with DEX achieved a statistically significant gain in BCVA measured in logMAR after 1xa0month (mean gain, 95% CI: 0.21, 0.08–0.34, pu2009=u20090.001), 3xa0months (0.16, 0.03–0.28, pu2009=u20090.012) and 6xa0months (0.19, 0.07–0.32, pu2009=u20090.002), whereas patients treated with IVR showed a statistically significant BCVA gain in month 3 (mean improvement, 95% CI: 0.13, 0.01–0.26, pu2009=u20090.039) and month 6 (0.16, 0.03–0.29, pu2009=u20090.018). BCVA in CRVO patients with DEX worsened slightly at month 6 (mean worsening, 95% CI: −0.08, −0.24 to 0.08, pu2009=u20090.305), while IVR treated-patients achieved a statistically significant BCVA gain at 3xa0months (mean improvement, 95% CI: 0.14, 0.02–0.25, pu2009=u20090.021). Both therapies were accompanied by statistically significant CRT reductions of 150 to 200xa0μm (median). Adverse events reported were predictable and limited.ConclusionsIn a clinical setting, comparable improvement in BCVA and CRT were observed after DEX and IVR injections for treatment of BRVO. CRVO patients showed greater benefit with IVR.

Immunosuppressants and/or antivascular endothelial growth factor inhibitors in punctate inner choroidopathy? Follow-up results with optical coherence tomography angiography

Purpose To report the effectiveness of treatment with antivascular endothelial growth factor (VEGF)-inhibitor and/or immunosuppressants in punctate inner choroidopathy (PIC) using standard imaging modalities and optical coherence tomography angiography (OCTA) over a time period of 16 months. Methods In this prospective, unmasked, single-centre study, 23 individuals with PIC underwent imaging with spectral domain OCT, fluorescein angiography, indocyanine green angiography and OCTA. Two groups were formed based on systemic treatment. In case of choroidal neovascularisation (CNV) activity, intravitreal anti-VEGF injections were carried out in both groups. Results Group I included 12 patients (24 eyes) with 18 affected eyes (75%) who did not receive any systemic therapy at baseline. Group II contained 11 patients (22 eyes) who started systemic immunosuppressive therapy on average 2 years before baseline. All eyes with recurrence of CNV or residual fluid (group I: seven eyes; group II: six eyes) received anti-VEGF agents. Group I showed a significant reduction of CNV size (p=0.0078), as well as a decrease of fluid retention (p=0.0078) on OCTA after anti-VEGF injection. Group II did not demonstrate any significant reduction of CNV size, vessel shape or fluid retention post injection. But overall, fluid accumulation was significantly lower in group II (median=0.03 mm2) than in group I (median=0.32 mm2) (p=0.0028). Conclusion Immunosuppressants in addition to anti-VEGF agents showed a significant reduction of fluid accumulation, that is, reduced disease activity. We conclude that there is a benefit and effectiveness of immunosuppressants to control inflammatory secondary CNV in PIC.