Publications by authors named "Thomas Ness"

49 Publications

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

Ocul Immunol Inflamm 2021 May 19:1-14. Epub 2021 May 19.

Eye and Vision Health section, Flinders University College of Medicine and Public Health, Adelaide, Australia.

: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL).: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations.: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended.: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.
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http://dx.doi.org/10.1080/09273948.2021.1878233DOI Listing
May 2021

Case Report: Blurred Vision and Eruptive Nevi - Bilateral Diffuse Uveal Melanocytic Proliferation With Mucocutaneous Involvement in a Lung Cancer Patient.

Front Oncol 2021 13;11:658407. Epub 2021 Apr 13.

Eye Center, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a "Cultured melanocyte elongation and proliferation (CMEP)" factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma should be considered making a thorough diagnostic workup mandatory.
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http://dx.doi.org/10.3389/fonc.2021.658407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076566PMC
April 2021

Developmental cell programs are co-opted in inflammatory skin disease.

Science 2021 01;371(6527)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK.

The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
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http://dx.doi.org/10.1126/science.aba6500DOI Listing
January 2021

Correction: Design, development, testing at ISO standards and in vivo feasibility study of a novel polymeric heart valve prosthesis.

Biomater Sci 2020 08 29;8(16):4639. Epub 2020 Jul 29.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.

Correction for 'Design, development, testing at ISO standards and in vivo feasibility study of a novel polymeric heart valve prosthesis' by Joanna R. Stasiak et al., Biomater. Sci., 2020, DOI: .
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http://dx.doi.org/10.1039/d0bm90064hDOI Listing
August 2020

Design, development, testing at ISO standards and in vivo feasibility study of a novel polymeric heart valve prosthesis.

Biomater Sci 2020 Aug 1;8(16):4467-4480. Epub 2020 Jul 1.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.

Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extra-vivo and in vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n = 8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n = 3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.
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http://dx.doi.org/10.1039/d0bm00412jDOI Listing
August 2020

[Ophthalmological Screening in Children and Adults with Intellectual Disability].

Klin Monbl Augenheilkd 2020 Aug 26;237(8):980-984. Epub 2020 May 26.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg.

Introduction: Special Olympics Germany is the German association of the largest global movement to provide year-round sports training and athletic competition in a variety of Olympic-type sports for children and adults with intellectual and multiple disabilities. We offered all participants ophthalmological screening during the event in Offenburg, Baden-Württemberg, in 2017 as part of the health programme "Open Eyes - Better Vision".

Methods: A team of optometrists took medical histories, examined refraction status, visual acuity, colour vision and orthoptic status. Four experienced physicians in training and specialists from the Eye Centre, University of Freiburg, performed slit-lamp examinations, funduscopy and eye pressure measurements. Dilated funduscopy and OCT were also performed, as necessary.

Results: In total, we screened 166 persons (48% female = 80; 52% male = 86). The cover test was abnormal in about 45% (distant) and 47% (near) of patients, respectively. Six and 11% of patients, respectively, complained of double vision (9/156; 17/156; distant and near). Reduced colour vision with nine of nine tables (Colour Vision Testing Made Easy by Waggoner) was recorded in 8% of patients (11/143). We saw fundus abnormalities in 13% of patients (16/125). 41% of patients (48/118) needed a prescription of new glasses. 29% of patients (45/157) were hypersensitive to light. 10% of patients (16/160) had never been examined by an ophthalmologist. In 4% of patients (7/166) we recommended urgent consultation of an ophthalmologist (e.g. in case of corneal hydrops or elevated intraocular pressure). We discussed possible treatment (mainly dry eye) in 40% (66/166).

Discussion: People with intellectual disabilities do not necessarily and directly complain about new vision problems or general problems with the eyes. In addition, there may be limited access to ophthalmological care compared to people without mental disabilities. Due to the four percent of diagnoses requiring treatment and 53% of participants who do not have current refraction compensation, ophthalmological monitoring of the Special Olympics eye program "Opening Eyes - Better Vision" seems to be an efficient mean for improving healthcare in this vulnerable group.
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http://dx.doi.org/10.1055/a-1141-3911DOI Listing
August 2020

[Prevention of Recurrence of Ocular Toxoplasmosis - When? How? For Whom?]

Klin Monbl Augenheilkd 2020 May 20;237(5):599-604. Epub 2020 May 20.

Berner Augenklinik am Lindenhofspital, Bern, Schweiz.

Background: Ocular toxoplasmosis (OT) leads to permanent visual disturbances in a high proportion of patients. A combination of antibiotics and corticosteroids may reduce the risk of permanent visual impairment and may delay recurrence. In this overview, we summarise the current state of knowledge regarding the recurrence prophylaxis of OT.

Method: The basis of this review is a literature search in PubMed with the key words (MeSH terms) "human ocular toxoplasmosis" or "retinochoroiditis" and "recurrence" and "prophylaxis" or "prevention". The resulting publications included case series with more than 20 patients, prospective clinical studies and meta-analyses published within the last 25 years, as well as other publications mentioned therein, and was evaluated on the basis of the experience of the authors.

Results: The frequency of recurrences does not differ between Latin America, North America and Europe, and is around 12 - 15% in the first two years and then decreases, with recurrences observed up to 49 years after an active infection. According to two placebo-controlled double-blind studies from Brazil, where particularly serious relapses occur, antibiotic prophylaxis with 160 mg trimethoprim combined with 800 mg sulfamethoxazole three times a week for 12 months can reduce the occurrence of relapses from 22 to 3% for up to three years. After that, the likelihood of recurrence is as high as in patients who have never received prophylaxis.

Conclusion: Relapses can be effectively prevented, if this is medically indicated. Among other considerations are central location of the lesion, insufficient immune competence and frequent relapses. Prophylaxis should be carried out for at least 12 months, since the risk of recurrence is highest in the first two years.
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http://dx.doi.org/10.1055/a-1141-3812DOI Listing
May 2020

Novel insights into retinal neovascularization secondary to central serous chorioretinopathy using 3D optical coherence tomography angiography.

Am J Ophthalmol Case Rep 2020 Jun 11;18:100609. Epub 2020 Feb 11.

Eye Center, Albert-Ludwig University Freiburg, Freiburg, Germany.

Purpose: To describe the clinical presentation and novel anatomical features of a patient with chronic central serous chorioretinopathy (CSCR) complicated by retinal neovascularization (RNV).

Observations: A 48 year-old patient with a long-standing history of bilateral CSCR presented to our clinic complaining about a sudden onset of tiny floaters. Multimodal imaging including fundus autofluorescence (FAF), fundus fluorescein (FA) and ICG angiography (ICG) and spectral domain optical coherence tomography (SD-OCT) confirmed the diagnosis of CSCR and revealed a pre-retinal neovascularization and concurring vitreous hemorrhage. Swept source OCT angiography (OCTA) and 3D reconstruction virtual reality determined the retinal origin of the neovascularization. Follow-up examination revealed clearing of the vitreous hemorrhage and spontaneous obliteration of the RNV without any treatment three months following the initial presentation.

Conclusion And Importance: To the best of our knowledge, this is the first report of a RNV associated with CSCR which was determined by three-dimensional (3D) OCTA reconstruction.
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http://dx.doi.org/10.1016/j.ajoc.2020.100609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036447PMC
June 2020

[Postoperative Quality Assurance After Cataract Surgery Via the Internet].

Klin Monbl Augenheilkd 2020 Jan 19;237(1):57-61. Epub 2019 Nov 19.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg.

Background: Numerous surgeries in the field of ophthalmology take place on an outpatient basis or only as part of a short inpatient stay. The quality requirements are very high. Postoperative quality controls often can't be done by surgeons themselves because the postoperative aftercare is usually no longer carried out at the surgical centre but by the referring ophthalmologists.

Methods: To optimize our operative quality assurance, the eye center of the University Hospital Freiburg has developed an internet-based quality assurance procedure in cooperation with the Augennetz Südbaden (ANSB), in which numerous established ophthalmologists from the region network. There is comprehensive reporting on cataract surgeries. The results of the follow-up examinations are reported in a structured manner via secure internet masks from the doctors' practices, taking into account data protection regulations. Feedback always takes place after 3 months and, thus, at a point in time at which the final surgical result can usually be assessed.

Results: Since the establishment of the quality register in November 2009, a total of 8043 records of cataract operations have been reported until the end of 2018. This sample comprises 20.2% of all cataract operations performed at the eye center of the University Hospital Freiburg during the same period. Mean follow-up was 76 days. During cataract surgery, the target refraction was missed by less than 1 dioptre in 90% of all operated eyes. Keratoplasty was identified as a risk factor for missing the target refraction.

Conclusion: The internet-based quality assurance of the eye center of the University Hospital Freiburg enables continuous monitoring of the operation quality over a longer period of time. In patients that underwent keratoplasty, the biometry should be critically questioned preoperatively.
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http://dx.doi.org/10.1055/a-1002-0208DOI Listing
January 2020

[Infections of the eye - what should internal specialists know?]

Dtsch Med Wochenschr 2019 10 8;144(20):1405-1410. Epub 2019 Oct 8.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg.

Infections can affect all structures of the eye. This article focuses on corneal and uveal infections, and on endophthalmitis. The typical pathogens, the signs and symptoms and the therapy are presented.
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http://dx.doi.org/10.1055/a-0655-8442DOI Listing
October 2019

[Eye involvement in large vesssel vasculitis (giant cell arteritis and Takayasu's arteritis)].

Ophthalmologe 2019 Sep;116(9):899-914

Rheumatologie, Klinische Immunologie und Osteologie, Standort Berlin-Buch, Immanuel Krankenhaus Berlin, Berlin, Deutschland.

Giant cell arteritis (GCA) and Takayasu's arteritis are both forms of large vessel vasculitis and can be manifested in the eye. While GCA affects patients over the age of 50 years, patients with Takayasu's arteritis are between 15 and 30 years old. The diagnosis is based on a combination of anamnesis, imaging and systemic inflammatory reactions. The diagnosis can be confirmed by biopsy. Typical eye involvement of GCA are anterior ischemic optic neuropathy (AION) and central retinal artery occlusion, while Takayasu's arteritis involves hypertensive retinopathy and Takayasu's retinopathy (capillary dilatation, microaneurysms and arteriovenous anastomoses). The treatment consists of steroids in combination with classical immunosuppressants or biologics.
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http://dx.doi.org/10.1007/s00347-019-00959-9DOI Listing
September 2019

Acute unilateral maculopathy associated with adult onset of hand, foot and mouth disease: a case report.

BMC Ophthalmol 2019 May 7;19(1):104. Epub 2019 May 7.

Eye Center, Faculty of Medicine, Albert-Ludwigs University Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Background: To report the case of a 31-year-old patient with Hand, Foot and Mouth Disease (HFMD) and concurrent acute monocular maculopathy, and to describe multimodal imaging findings never before described including optical coherence tomography angiography (OCT-A).

Case Presentation: Nine days after the onset of clinically highly probable but not laboratory-verified HFMD, a 31-year old male noticed a central scotoma, distorted lines and loss of visual acuity (Snellen visual acuity 20/400) in his right eye. Funduscopy revealed focal alterations in the retinal pigmented epithelium (RPE) and yellow retinal dots corresponding to focal dots of decreased fundus autofluorescence (FAF) surrounded by increased FAF. Spectral domain optical coherence tomography (SD-OCT) demonstrated irregularities in the ellipsoide zone, hyperreflective dots above the RPE and RPE thickening. Fundus fluorescein angiography (FAG) revealed central hypofluorescence in the macular area in the early phase, as well as increasing focal hyperfluorescence in the late phase corresponding with RPE defects observed in FAF. Indocyanine green angiography (ICGA) showed central hypofluorescence in the early and late phase, corresponding with areas of reduced flow in the choroidea and choriocapillaris as apparent in OCT-A. Visual acuity improved within 3 months without any systemic or local therapy. At his three-month follow-up, SD-OCT revealed subtle subretinal fluid that resolved spontaneously over time. No signs of choroidal neovascularization were observed. Twelve months following the onset of symptoms Snellen visual acuity was 400/400. Multimodal imaging revealed subtly changed, decreased FAF while the choroidal architecture recovered completely as demonstrated by OCT-A.

Conclusions: HFMD-associated maculopahty is an uncommon but important differential diagnosis of chorioretinitis with macular involvement. The prognosis can be good and the initially observed morphological pathologies such as impaired perfusion of the choroidal vessels can recover spontaneously over a period lasting 12 months. OCT-A can be employed as a non-invasive tool to detect the reduced perfusion of the choroidal vessels and for monitoring the disease course.
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http://dx.doi.org/10.1186/s12886-019-1111-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505311PMC
May 2019

[Progressive loss of vision in cone dystrophy. Search for evidence with macular OCT and multifocal ERG].

Ophthalmologe 2019 Aug;116(8):789-793

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Deutschland.

A 53-year-old patient consulted our practice clinic complaining of progressive visual loss, increased glare sensitivity and color sense disorder. Extensive diagnostic investigation, including multifocal ERG (mfERG) and macular thickness map with the help of optical coherence tomography (OCT), supported the suspected diagnosis of a cone dystrophy. There are, however, no established therapeutic options. A diagnostic confirmation by means of molecular genetics was not successful.
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http://dx.doi.org/10.1007/s00347-018-0804-zDOI Listing
August 2019

Moose at their bioclimatic edge alter their behavior based on weather, landscape, and predators.

Curr Zool 2018 Aug 28;64(4):419-432. Epub 2017 Jul 28.

Conservation Department, Minnesota Zoo, 13000 Zoo Boulevard, Apple Valley, MN, USA.

Populations inhabiting the bioclimatic edges of a species' geographic range face an increasing amount of stress from alterations to their environment associated with climate change. Moose are large-bodied ungulates that are sensitive to heat stress and have exhibited population declines and range contractions along their southern geographic extent. Using a hidden Markov model to analyze movement and accelerometer data, we assigned behaviors (rest, forage, or travel) to all locations of global positioning system-collared moose (13, moose-years = 19) living near the southern edge of the species' range in and around Voyageurs National Park, MN, USA. We assessed how moose behavior changed relative to weather, landscape, and the presence of predators. Moose significantly reduced travel and increased resting behaviors at ambient temperatures as low as 15 °C and 24 °C during the spring and summer, respectively. In general, moose behavior changed seasonally in association with distance to lakes and ponds. Moose used wetlands for travel throughout the year, rested in conifer forests, and foraged in shrublands. The influence of wolves varied among individual moose and season, but the largest influence was a reduction in travel during spring when near a wolf home range core, primarily by pregnant females. Our analysis goes beyond habitat selection to capture how moose alter their activities based on their environment. Our findings, along with climate change forecasts, suggest that moose in this area will be required to further alter their activity patterns and space use in order to find sufficient forage and avoid heat stress.
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http://dx.doi.org/10.1093/cz/zox047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084617PMC
August 2018

[Endophthalmitis].

Authors:
Thomas Neß

Ophthalmologe 2018 Aug;115(8):697-706

Klinik für Augenheilkunde, Medizinische Fakultät, Universitätsklinikum Freiburg, Killianstr. 5, 79106, Freiburg, Deutschland.

Endophthalmitis is a severe intraocular infection with potentially devastating consequences, such as becoming blind or loss of an eyeball. It can be exogenous (postoperative or posttraumatic) or endogenous. The most frequent causes of postoperative endophthalmitis are cataract surgery and intravitreal injections. Typical symptoms are pain and loss of visual acuity. Hypopyon and infiltration of the vitreous body with the loss of the red reflex are the most important clinical findings for endophthalmitis. The diagnosis is primarily clinical and supported by microbiological cultures and PCR from the vitreous body and/or anterior chamber and is of use for a targeted treatment. Treatment is a combination of intravitreal, systemic, and topical antibiotics, anterior chamber lavage, and vitrectomy. The decisive factor for the prognosis is the triggering pathogen. Infections with coagulase-negative staphylococci or Candida spp. have a good prognosis. Infections with Streptococcus spp., Bacillus spp. or Aspergillus spp. are unfavorable.
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http://dx.doi.org/10.1007/s00347-018-0729-6DOI Listing
August 2018

[Systemic Corticosteroids in Non-infectious Uveitis].

Authors:
Thomas Neß

Klin Monbl Augenheilkd 2018 May 8;235(5):592-596. Epub 2018 May 8.

Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg.

Corticosteroids are essential in the treatment of non-infectious uveitis, rheumatic diseases, autoimmune diseases, allergy, and in the therapy and prevention of transplant rejection. In addition to their beneficial effects, corticosteroids may have various adverse events, even with long-term use. Therefore, therapy with corticosteroids necessitates adequate dosing, monitoring and prophylaxis.
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http://dx.doi.org/10.1055/a-0596-7593DOI Listing
May 2018

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

Br J Ophthalmol 2018 05 13;102(5):647-653. Epub 2017 Sep 13.

Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.

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.
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http://dx.doi.org/10.1136/bjophthalmol-2017-310156DOI Listing
May 2018

Switch of Intravitreal Therapy for Macular Edema Secondary to Retinal Vein Occlusion from Anti-VEGF to Dexamethasone Implant and Vice Versa.

J Ophthalmol 2017 30;2017:5831682. Epub 2017 Jul 30.

University Eye Hospital, Hanover Medical School, Hanover, Germany.

Purpose: To evaluate the anatomical and functional outcome of intravitreal dexamethasone implant for macular edema secondary to central (C) or branch (B) retinal vein occlusion (RVO) in patients with persistent macular edema (ME) refractory to intravitreal antivascular endothelial growth factor (VEGF) treatment compared to treatment naïve patients and to dexamethasone-refractory eyes switched to anti-VEGF.

Methods: Retrospective, observational study including 30 eyes previously treated with anti-VEGF (8 CRVO, 22 BRVO, mean age 69 ± 10 yrs), compared to 11 treatment naïve eyes (6 CRVO, 5 BRVO, 73 ± 11 yrs) and compared to dexamethasone nonresponders (2 CRVO, 4 BRVO, 69 ± 12). Outcome parameters were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by spectral-domain optical coherence tomography.

Results: Mean BCVA improvement after switch to dexamethasone implant was 4 letters ( = 0.08), and treatment naïve eyes gained 10 letters ( = 0.66), while we noted no change in eyes after switch to anti-VEGF ( = 0.74). Median CFT decrease was most pronounced in treatment naïve patients (-437 m, = 0.002) compared to anti-VEGF refractory eyes (-170 m, = 0.003) and dexamethasone-refractory eyes (-157, = 0.31).

Conclusions: Dexamethasone significantly reduced ME secondary to RVO refractory to anti-VEGF. Functional gain was limited compared to treatment naïve eyes, probably due to worse BCVA and CFT at baseline in treatment naïve eyes.
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http://dx.doi.org/10.1155/2017/5831682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554567PMC
July 2017

Intermediate uveitis: pattern of etiology, complications, treatment and outcome in a tertiary academic center.

Orphanet J Rare Dis 2017 04 27;12(1):81. Epub 2017 Apr 27.

Eye Center, Medical Center, University of Freiburg, Faculty of Medicine, Killianstr. 5, 79106, Freiburg, Germany.

Background: Patients with intermediate uveitis (IU) represent a heterogenous group characterized by a wide spectrum of etiologies and regional differences. Aim of the study was to analyze the characteristics of patients with IU examined in an academic center in Germany.

Methods: We conducted a retrospective analysis of the clinical records of all patients with intermediate uveitis referred to the Eye Center, University of Freiburg from 2007 to 2014. Diagnosis followed the Standardization in Uveitis Nomenclature (SUN) criteria. Data analysis included: etiology of IU, demographics, complications, treatment and visual acuity.

Results: We identified 159 patients with intermediate uveitis during that period. Mean age at diagnosis was 35 years. Most are female (64%), and the mean duration of IU was 6.1 years (range 1 month - 35 years). Etiology of IU was idiopathic in 59%. Multiple sclerosis (MS) (20%) and sarcoidosis (10%) were frequent systemic causes of IU. Other etiologies including infectious diseases (tuberculosis, borreliosis) or immune-mediated conditions (eg, after vaccination) were present in 11%. The pattern of complications included macular edema (CME) (36%), cataract (24%), secondary glaucoma (7%), and epiretinal membrane formation (19%). Periphlebitis and optic neuritis were more frequent in conjunction with MS. Treatment comprised local and systemic steroids, immunosuppressive agents, biologics, and surgery. Best corrected visual acuity was better than 20/25 in 60% of the eyes after more than 10 years of follow-up.

Conclusions: In our German academic center, most IU cases were idiopathic or associated with MS or sarcoidosis. In contrast to other countries, infectious cases were rare. Patients' overall visual prognosis is favorable even when the duration of IU has been long and and despite numerous complications.
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http://dx.doi.org/10.1186/s13023-017-0638-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408401PMC
April 2017

DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas.

Cell 2016 11 27;167(5):1264-1280.e18. Epub 2016 Oct 27.

Department of Pathology, Schleswig-Holstein University Hospital, Campus Lübeck and Research Center Borstel, 23845 Borstel, Germany.

Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent inflammatory stimuli, pathways previously linked to oncogene-initiated carcinogenesis instruct a long-lived granuloma-resident macrophage differentiation program that regulates granulomatous tissue remodeling.
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http://dx.doi.org/10.1016/j.cell.2016.09.054DOI Listing
November 2016

Secondary Antibody Deficiency in Glucocorticoid Therapy Clearly Differs from Primary Antibody Deficiency.

J Clin Immunol 2016 05 15;36(4):406-12. Epub 2016 Mar 15.

Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg, Breisacher Str. 117, 79106, Freiburg, Germany.

Purpose: The aim of this study was to identify characteristics of hypogammaglobulinemia secondary to glucocorticoid therapy and their value in the differential diagnosis to primary forms of antibody deficiency.

Methods: We investigated prevalence and character of hypogammaglobulinemia in a cohort of 36 patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) on glucocorticoid therapy in comparison to a gender- and age-matched cohort of hospital controls. We therefore determined serum immunoglobulin levels as well as B- and T cell-subsets in the peripheral blood of all participants. In addition, prior serum immunoglobulin levels and clinical data of the GCA and PMR patients were extracted from the electronic patient data-base.

Results: 21/36 GCA/PMR patients on glucocorticoid treatment developed antibody deficiency. In 19 patients this included IgG and in 13 patients IgG was the only affected isotype. The reduction of IgG was persistent in nearly 50 % of these patients during the observed period. GCA/PMR patients had reduced circulating naive and transitional B cells (p = 0.0043 and p = 0.0002 respectively) while IgM, IgG and IgA memory B cells were preserved. Amongst T-cell subsets, we found a reduction of CD4 memory T cells (p < 0.0001), CD4 regulatory T cells (p = 0.0002) and few CD8 memory T-cell subtypes.

Conclusion: Persistent humoral immunodeficiency occurs in about a quarter of GCA/PMR patients under glucocorticoid therapy. Because most patients have isolated IgG deficiency, preserved IgA production and class-switched memory B cells, by these markers this form of secondary hypogammaglobulinemia can be clearly distinguished from common variable immunodeficiency (CVID).
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http://dx.doi.org/10.1007/s10875-016-0264-7DOI Listing
May 2016

Interleukin-2 Receptor and Angiotensin-Converting Enzyme as Markers for Ocular Sarcoidosis.

PLoS One 2016 22;11(1):e0147258. Epub 2016 Jan 22.

Eye Center, University Hospital Freiburg, Freiburg, Germany.

Purpose: To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients.

Design: Retrospective study.

Methods: Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis.

Main Outcome Measure: Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis.

Results: We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis.

Conclusions: An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147258PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723126PMC
August 2016

Acute Retinal Necrosis: Diagnostic and Treatment Strategies in Germany.

Ocul Immunol Inflamm 2016 Oct 23;24(5):537-43. Epub 2015 Sep 23.

e University Eye Center, University Hospital of Freiburg , Freiburg , Germany.

Purpose: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany.

Methods: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009.

Results: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%.

Conclusions: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline.
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http://dx.doi.org/10.3109/09273948.2015.1034375DOI Listing
October 2016

Trabeculectomy ab interno with the Trabectome® as a therapeutic option for uveitic secondary glaucoma.

Graefes Arch Clin Exp Ophthalmol 2015 Nov 24;253(11):1973-8. Epub 2015 Jul 24.

Eye Center, University of Freiburg, Killianstraße 5, 79106, Freiburg, Germany.

Purpose: Treatment of secondary glaucoma in uveitis patients is challenging. Owing to the young age of these patients, sufficient lowering of the intraocular pressure (IOP) is essential to prevent progression of visual field loss. However, because of the chronic inflammatory stimulus, filtration surgery has an increased risk of failure, especially in patients who have previously undergone surgery. Therefore, minimally invasive glaucoma surgery is a valuable alternative.

Methods: The clinical records of 24 consecutive patients with uveitic secondary glaucoma who underwent trabeculectomy ab interno with the Trabectome® at the Eye Center of the Albert-Ludwigs University of Freiburg between June 2009 and June 2014 (registered in the Freiburg trabectome database) were retrospectively analyzed. The general baseline information for each patient included age, gender, glaucoma type, ocular medication and current IOP. The postoperative IOP and number of antiglaucomatous medications were recorded at each visit. Statistical analyses were performed using the Kaplan-Meier estimator and Dunnett's t-test.

Results: The mean IOP before surgery was 31 ± 6.7 mmHg (median 32 mmHg). Both the IOP and the number of medications significantly decreased over the various follow-up intervals after trabeculectomy ab interno with the Trabectome®. Patients with follow-ups continuing past one year showed an IOP-reduction of approximately 40 % and a medication number reduction from 2 to 0.67. The failure rate (necessitating further glaucoma surgery) was N = 3 (12.5 %) patients.

Conclusions: Trabeculectomy ab interno with the Trabectome® is a minimally invasive and effective method for controlling IOP in uveitic secondary glaucoma.
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http://dx.doi.org/10.1007/s00417-015-3102-3DOI Listing
November 2015

Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.

Clin Epigenetics 2015 14;7:25. Epub 2015 Mar 14.

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.

Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patients. Currently, it is not clear which factors determine progression to fibrosis. We investigated whether DNA\methylation profile as determined by pyrosequencing can distinguish patients with mild from those with advanced/severe fibrosis in non-alcoholic liver disease (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liver biopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite converted and pyrosequencing assays used to quantify DNA methylation at specific CpGs within PPARα, PPARα, TGFβ1, Collagen 1A1 and PDGFα genes. Furthermore, we assessed the impact of age, gender and anatomical location within the liver on patterns of DNA methylation in the same panel of genes.

Results: DNA methylation at specific CpGs within genes known to affect fibrogenesis distinguishes between patients with mild from those with severe fibrosis in both NAFLD and ALD, although same CpGs are not equally represented in both etiologies. In normal liver, age, gender or anatomical location had no significant impact on DNA methylation patterns in the liver.

Conclusions: DNA methylation status at specific CpGs may be useful as part of a wider set of patient data for predicting progression to liver fibrosis.
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http://dx.doi.org/10.1186/s13148-015-0056-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391139PMC
April 2015

Ocular changes during pregnancy.

Dtsch Arztebl Int 2014 Aug;111(33-34):567-75; quiz 576

Interdisciplinary Uveitis Center, Department of Ophthalmology, University of Heidelberg, Institute of Reproductive Toxicology Ravensburg, Department of Internal Medicine V, Department of Ophthalmology, University of Freiburg i. Brsg.

Background: Most ocular changes in pregnancy are harmless. For example, 14% of pregnant women need a new eyeglass prescription. Some changes, however, are serious, such as retinal effects of hypertension, which can be a sign of pre-eclampsia. Ocular changes may give rise to uncertainty about the administration of ophthalmological drugs or the optimal method of childbirth.

Method: This review is based on pertinent literature retrieved by a selective search in Medline and on guidelines from Germany and abroad. Recommendations about drugs were taken from the Embryotox and Reprotox databases, the German Red List, and the United States Food and Drug Administration (FDA).

Results: 40% to 100% of pregnant women with high blood pressure have retinal changes whose severity is correlated with the severity of pre-eclampsia or eclampsia. Diabetic women should undergo ocular examination before and during pregnancy. Pre-existing retinal changes worsen during pregnancy in 55% of cases. Most ocular diseases can be treated with the usual drugs in pregnant women and nursing mothers, although the evidence for drug safety is derived from case series and the treatment is usually provided off label. Ocular conditions that are present before pregnancy are irrelevant to the choice of a method of childbirth.

Conclusion: Pregnant women and nursing mothers can undergo most types of ophthalmological examination and treatment. Recommendations about drug treatment should be checked against current information that can be found on the embryotox.de and reprotox.de websites.
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http://dx.doi.org/10.3238/arztebl.2014.0567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165189PMC
August 2014

The trabectome as treatment option in secondary glaucoma due to intraocular lymphoma.

J Glaucoma 2014 Sep;23(7):482-4

*University Eye Hospital †Department of Hematology and Oncology, University Hospital Medical Center, Freiburg, Germany.

Primary intraocular lymphoma can cause an elevation of intraocular pressure (IOP), resulting from infiltration of the trabecular meshwork with neoplastic lymphocytes. More rarely, therapeutic procedures can induce a highly synchronised death of tumor cells, leading to congestion of the trabecular meshwork with cell debris. We report on a case of severe IOP elevation after intraocular therapy with methotrexate and rituximab. As medical glaucoma therapy failed, a trabeculotomy with the trabectome was performed, leading to an immediate and sustained decrease in IOP. This novel approach is discussed considering pathogenic aspects of lymphoma-associated glaucoma and alternative surgical techniques.
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http://dx.doi.org/10.1097/IJG.0b013e31827a0875DOI Listing
September 2014