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1.
Cell ; 167(5): 1264-1280.e18, 2016 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-28084216

RESUMEN

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.


Asunto(s)
Daño del ADN , Granuloma/inmunología , Macrófagos/inmunología , Mycobacterium tuberculosis/inmunología , Animales , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Diferenciación Celular , Proliferación Celular , Humanos , Inflamación/inmunología , Lipoproteínas/inmunología , Ratones , Ratones Endogámicos C57BL , Mitosis , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptor Toll-Like 2
3.
Nature ; 598(7880): 327-331, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34588693

RESUMEN

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).


Asunto(s)
Células de la Médula Ósea/citología , Médula Ósea , Síndrome de Down/sangre , Síndrome de Down/inmunología , Feto/citología , Hematopoyesis , Sistema Inmunológico/citología , Linfocitos B/citología , Células Dendríticas/citología , Síndrome de Down/metabolismo , Síndrome de Down/patología , Células Endoteliales/patología , Eosinófilos/citología , Células Eritroides/citología , Granulocitos/citología , Humanos , Inmunidad , Células Mieloides/citología , Células del Estroma/citología
4.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 937-948, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37855957

RESUMEN

PURPOSE: To evaluate the efficacy of XEN®-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma. METHODS: Retrospective analysis of 25 eyes receiving XEN® gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN® implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure. RESULTS: Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success. CONCLUSION: The XEN® gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes.


Asunto(s)
Glaucoma , Humanos , Estudios Retrospectivos , Glaucoma/etiología , Glaucoma/cirugía , Presión Intraocular , Tonometría Ocular , Conjuntiva , Antihipertensivos/uso terapéutico
5.
Klin Monbl Augenheilkd ; 241(5): 644-652, 2024 May.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-38593832

RESUMEN

Giant cell arteritis (GCA) is the most common primary vasculitis and is associated with potential bilateral blindness. Neither clinical nor laboratory evidence is simple and unequivocal for this disease, which usually requires rapid and reliable diagnosis and therapy. The ophthalmologist should consider GCA with the following ocular symptoms: visual loss or visual field defects, transient visual disturbances (amaurosis fugax), diplopia, eye pain, or new onset head or jaw claudication. An immediate ophthalmological examination with slit lamp, ophthalmoscopy, and visual field, as well as color duplex ultrasound of the temporal artery should be performed. If there is sufficient clinical suspicion of GCA, corticosteroid therapy should be initiated immediately, with prompt referral to a rheumatologist/internist and, if necessary, temporal artery biopsy should be arranged. Numerous developments in modern imaging with colour duplex ultrasonography, MRI, and PET-CT have the potential to compete with the classical, well-established biopsy of a temporal artery. Early determination of ESR and CRP may support RZA diagnosis. Therapeutically, steroid-sparing immunosuppression with IL-6 blockade or methotrexate can be considered. These developments have led to a revision of both the classification criteria and the diagnostic and therapeutic recommendations of the American College of Rheumatologists and the European League against Rheumatism, which are summarised here for ophthalmology.


Asunto(s)
Arteritis de Células Gigantes , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/terapia , Humanos , Diagnóstico Diferencial , Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Arterias Temporales/patología , Arterias Temporales/diagnóstico por imagen , Medicina Basada en la Evidencia , Resultado del Tratamiento , Biopsia
6.
Klin Monbl Augenheilkd ; 241(5): 633-643, 2024 May.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-38776930

RESUMEN

Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.


Asunto(s)
Úlcera de la Córnea , Inmunosupresores , Humanos , Diagnóstico Diferencial , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/terapia , Úlcera de la Córnea/etiología , Inmunosupresores/uso terapéutico
7.
J Eur Acad Dermatol Venereol ; 37(3): 605-614, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36367625

RESUMEN

BACKGROUND: The application of artificial intelligence (AI) to whole slide images has the potential to improve research reliability and ultimately diagnostic efficiency and service capacity. Image annotation plays a key role in AI and digital pathology. However, the work-streams required for tissue-specific (skin) and immunostain-specific annotation has not been extensively studied compared with the development of AI algorithms. OBJECTIVES: The objective of this study is to develop a common workflow for annotating whole slide images of biopsies from inflammatory skin disease immunostained with a variety of epidermal and dermal markers prior to the development of the AI-assisted analysis pipeline. METHODS: A total of 45 slides containing 3-5 sections each were scanned using Aperio AT2 slide scanner (Leica Biosystems). These slides were annotated by hand using a commonly used image analysis tool which resulted in more than 4000 images blocks. We used deep learning (DL) methodology to first sequentially segment (epidermis and upper dermis), with the exclusion of common artefacts and second to quantify the immunostained signal in those two compartments of skin biopsies and the ratio of positive cells. RESULTS: We validated two DL models using 10-fold validation runs and by comparing to ground truth manually annotated data. The models achieved an average (global) accuracy of 95.0% for the segmentation of epidermis and dermis and 86.1% for the segmentation of positive/negative cells. CONCLUSIONS: The application of two DL models in sequence facilitates accurate segmentation of epidermal and dermal structures, exclusion of common artefacts and enables the quantitative analysis of the immunostained signal. However, inaccurate annotation of the slides for training the DL model can decrease the accuracy of the output. Our open source code will facilitate further external validation across different immunostaining platforms and slide scanners.


Asunto(s)
Inteligencia Artificial , Enfermedades de la Piel , Humanos , Inmunohistoquímica , Reproducibilidad de los Resultados , Programas Informáticos
8.
Int Ophthalmol ; 43(7): 2397-2405, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36670265

RESUMEN

PURPOSE: Single center study to evaluate the incidence and long-term outcome of laser pointer maculopathy (LPM). METHODS: Medical records of 909,150 patients visiting our institution between 2007 and 2020 were screened in our electronic patient record system using the keywords "laserpointer," "laser pointer," and "solar." RESULTS: Eight patients (6/2 male/female, 11 eyes) with a history of LPM were identified by fundoscopy and optical coherence tomography (OCT), all of whom were children (6/2 male/female). Mean age at injury was 12.1 years (range 6-16). Five children (62.5%) were injured between 2019 and 2020, three (37.5%) between 2007 and 2018. Median best-corrected visual acuity (BCVA) of affected eyes at first presentation was 20/25 (range 20/50-20/16). Follow-up examination was performed in seven children (10 eyes) with a median follow-up period of 18 months (range 0.5-96). BCVA improved in 4 children (5 eyes; BCVA at follow-up 20/22.5, range 20/40-20/16). Three of these four children were treated with oral steroids. OCT revealed acute signs such as intraretinal fluid to resolve quickly, while outer retinal disruption persisted until the last follow-up in eight of eleven eyes. These lesions resembled lesions of patients with solar retinopathy of which seven cases (11 eyes) were identified between 2007 and 2020. CONCLUSION: Readily available consumer laser pointers can damage the retina and the underlying retinal pigment epithelium, possibly leading to long-lasting visual impairments. The number of laser pointer injuries has increased over the last years. Therefore, access to laser pointers for children should be strictly controlled.


Asunto(s)
Degeneración Macular , Enfermedades de la Retina , Humanos , Femenino , Masculino , Niño , Adolescente , Incidencia , Agudeza Visual , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/etiología , Rayos Láser , Degeneración Macular/complicaciones , Tomografía de Coherencia Óptica/métodos
9.
Graefes Arch Clin Exp Ophthalmol ; 260(9): 2991-3000, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35254510

RESUMEN

INTRODUCTION: Uveitic glaucoma remains challenging despite medical and surgical advancements and can potentially lead to blindness if left uncontrolled. Conservative alternatives as well as microinvasive surgeries can postpone the necessity of a highly invasive intervention. However, such procedures are still necessary to treat some refractive glaucoma cases. Since previous studies have reported excellent results following the primary implantation of glaucoma drainage devices, it was our study's aim to evaluate long-term results following a Baerveldt 250 implantation in highly complex and surgically burdened uveitic glaucoma eyes (UG) and compare these to a similar population suffering from other forms of glaucoma (OFG). MATERIAL AND METHODS: We performed a retrospective analysis of all eyes (UG vs. OFG) following a Baerveldt 250 implant between 2013 and 2019. Efficacy parameters as well as post-operative complication data were extracted from our electronic data system for statistical analysis. RESULTS: A total of 62 eyes were included in our study (24 UG and 38 OFG). UG baseline mean IOP was 35.04 mmHg (± 11.85 mmHg) with 3.08 (± 1.13) topical agents, and OFG was 32.63 mmHg (± 7.74 mmHg) with 2.68 (± 1.28) topical agents. A majority of eyes also required systemic acetazolamide (UG: 79% OFG: 87%) and had undergone at least one glaucoma-related operation prior to the Baerveldt 250 implant ((UG: 1.21 (± 0.66)), OFG: 1.74 (± 1.33)). At the median follow-up period (UG 592, OFG 764 days), 52.5%/32.5% of UG/OFG cases showed qualified success (IOP below 21 mmHg with either topical or/and systemic medication), 15%/30% no longer required topical medication, and 47.5% /47.5% were free of acetazolamide systemically. Moreover, 75%/72.5% of eyes experienced no further pressure-related surgical event. Although sight-threatening complications such as corneal and macular edema were reported in both groups, most either maintained or improved their visual acuity at the last follow-up (58.33%/57.89%). CONCLUSION: The Baerveldt 250 implant is shown to be both effective and safe for advanced glaucoma cases in uveitis and other forms. No further glaucoma-related surgery is required in the majority of eyes in either group within a follow-up period of almost 2 years. Despite sight-threatening complications such as macular and corneal edema, visual acuity can be either maintained or improved in most eyes.


Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma , Uveítis , Acetazolamida , Estudios de Seguimiento , Humanos , Presión Intraocular , Complicaciones Posoperatorias , Implantación de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento
10.
Klin Monbl Augenheilkd ; 239(5): 666-675, 2022 May.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-35320874

RESUMEN

Toxoplasma gondii, Treponema pallidum and Mycobacterium tuberculosis are the most important infectious causes of posterior uveitis. The epidemiology, clinical picture, diagnostic and treatment strategies of these diseases are presented.


Asunto(s)
Infecciones del Ojo , Toxoplasma , Toxoplasmosis Ocular , Toxoplasmosis , Tuberculosis , Uveítis Posterior , Uveítis , Infecciones del Ojo/complicaciones , Humanos , Toxoplasmosis Ocular/diagnóstico , Toxoplasmosis Ocular/terapia , Treponema , Uveítis/diagnóstico , Uveítis/etiología , Uveítis/terapia , Uveítis Posterior/diagnóstico , Uveítis Posterior/terapia
11.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-34731897

RESUMEN

BACKGROUND: Especially in rural areas, access of visually impaired people to ophthalmic care and counselling can be limited. The Eye Van is a project supported by the Ministry for Rural Affairs and Consumer Protection Baden-Württemberg which offers visually impaired people an on-the-spot ophthalmological examination and counselling on low-vision aids and social support services. The aim of this project was to evaluate the quality of care provided to visually impaired people in the rural areas of South Baden. MATERIALS AND METHODS: Between 2016 and 2019, 45 villages in South Baden participated in this project. The visits were advertised in the local press. Appointments were assigned and participant eligibility was assessed over the telephone by the local Federation of the Blind and Partially Sighted in South Baden. During the on-site visits, a medical history was obtained from participants, who then received a comprehensive ophthalmological examination and counselling on low-vision aids and social support services. Interviews were conducted in order to determine the expectations of the participants and to assess their quality of life. A second interview, focused on the measures that had been implemented and changes in the participants' quality of life, was carried out three months later. RESULTS: In total, 264 participants were examined. Of these, 101 participants fulfilled the criteria of moderate/severe visual impairment or blindness defined by the WHO (World Health Organization). The mean age of the visually impaired participants was 85 years. The median decimal visual acuity was 0.08. The median length of time since the participants' last ophthalmological examination was one year. Among the visually impaired participants, 13% did not have any low-vision aids. Their use was recommended to 62% of the visually impaired participants. The main expectation of participants was counselling on low-vision aids and support services. Among all the participants, 42 did one interview and 28 did two interviews. In the second interview, 72% of the participants claimed to have implemented the recommendations. There was no statistically significant change in their quality of life. CONCLUSION: The access of visually impaired people to ophthalmic care does not seem to be limited in the rural areas of South Baden. Nevertheless, there was a high demand for counselling on low-vision aids and social support services.

12.
Klin Monbl Augenheilkd ; 237(5): 599-604, 2020 May.
Artículo en Alemán | MEDLINE | ID: mdl-32434243

RESUMEN

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.


Asunto(s)
Coriorretinitis , Toxoplasmosis Ocular , Europa (Continente) , Humanos , Estudios Prospectivos , Recurrencia , Toxoplasmosis Ocular/epidemiología , Toxoplasmosis Ocular/prevención & control
13.
Klin Monbl Augenheilkd ; 237(1): 57-61, 2020 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-31745945

RESUMEN

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.


Asunto(s)
Extracción de Catarata , Catarata , Garantía de la Calidad de Atención de Salud , Biometría , Humanos , Internet , Periodo Posoperatorio
14.
Klin Monbl Augenheilkd ; 237(8): 980-984, 2020 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-32455447

RESUMEN

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.


Asunto(s)
Discapacidad Intelectual , Adulto , Niño , Alemania , Humanos , Trastornos de la Visión , Selección Visual , Pruebas de Visión , Agudeza Visual
15.
BMC Ophthalmol ; 19(1): 104, 2019 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-31064339

RESUMEN

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.


Asunto(s)
Enfermedades de la Coroides/virología , Enfermedad de Boca, Mano y Pie/complicaciones , Enfermedades de la Retina/virología , Adulto , Coroides/irrigación sanguínea , Humanos , Masculino , Escotoma/virología
17.
Klin Monbl Augenheilkd ; 235(5): 592-596, 2018 May.
Artículo en Alemán | MEDLINE | ID: mdl-29739029

RESUMEN

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.


Asunto(s)
Enfermedades Autoinmunes , Inmunosupresores , Uveítis , Corticoesteroides/uso terapéutico , Rechazo de Injerto , Humanos , Inmunosupresores/uso terapéutico , Uveítis/tratamiento farmacológico
18.
J Clin Immunol ; 36(4): 406-12, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26980224

RESUMEN

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).


Asunto(s)
Agammaglobulinemia/inducido químicamente , Arteritis de Células Gigantes/inmunología , Glucocorticoides/efectos adversos , Polimialgia Reumática/inmunología , Prednisona/efectos adversos , Agammaglobulinemia/sangre , Agammaglobulinemia/epidemiología , Agammaglobulinemia/inmunología , Anciano , Anciano de 80 o más Años , Subgrupos de Linfocitos B/inmunología , Femenino , Arteritis de Células Gigantes/sangre , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/epidemiología , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas/sangre , Masculino , Persona de Mediana Edad , Polimialgia Reumática/sangre , Polimialgia Reumática/tratamiento farmacológico , Polimialgia Reumática/epidemiología , Prednisona/uso terapéutico , Prevalencia , Subgrupos de Linfocitos T/inmunología
19.
Graefes Arch Clin Exp Ophthalmol ; 253(11): 1973-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26205735

RESUMEN

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.


Asunto(s)
Glaucoma de Ángulo Abierto/cirugía , Malla Trabecular/cirugía , Trabeculectomía/métodos , Uveítis Anterior/cirugía , Uveítis Intermedia/cirugía , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/etiología , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Tonometría Ocular , Uveítis Anterior/complicaciones , Uveítis Anterior/fisiopatología , Uveítis Intermedia/complicaciones , Uveítis Intermedia/fisiopatología , Campos Visuales/fisiología
20.
Radiology ; 273(3): 844-52, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25102371

RESUMEN

PURPOSE: To assess the diagnostic accuracy of contrast material-enhanced magnetic resonance (MR) imaging of superficial cranial arteries in the initial diagnosis of giant cell arteritis ( GCA giant cell arteritis ). MATERIALS AND METHODS: Following institutional review board approval and informed consent, 185 patients suspected of having GCA giant cell arteritis were included in a prospective three-university medical center trial. GCA giant cell arteritis was diagnosed or excluded clinically in all patients (reference standard [final clinical diagnosis]). In 53.0% of patients (98 of 185), temporal artery biopsy ( TAB temporal artery biopsy ) was performed (diagnostic standard [ TAB temporal artery biopsy ]). Two observers independently evaluated contrast-enhanced T1-weighted MR images of superficial cranial arteries by using a four-point scale. Diagnostic accuracy, involvement pattern, and systemic corticosteroid ( sCS systemic corticosteroid ) therapy effects were assessed in comparison with the reference standard (total study cohort) and separately in comparison with the diagnostic standard TAB temporal artery biopsy ( TAB temporal artery biopsy subcohort). Statistical analysis included diagnostic accuracy parameters, interobserver agreement, and receiver operating characteristic analysis. RESULTS: Sensitivity of MR imaging was 78.4% and specificity was 90.4% for the total study cohort, and sensitivity was 88.7% and specificity was 75.0% for the TAB temporal artery biopsy subcohort (first observer). Diagnostic accuracy was comparable for both observers, with good interobserver agreement ( TAB temporal artery biopsy subcohort, κ = 0.718; total study cohort, κ = 0.676). MR imaging scores were significantly higher in patients with GCA giant cell arteritis -positive results than in patients with GCA giant cell arteritis -negative results ( TAB temporal artery biopsy subcohort and total study cohort, P < .001). Diagnostic accuracy of MR imaging was high in patients without and with sCS systemic corticosteroid therapy for 5 days or fewer (area under the curve, ≥0.9) and was decreased in patients receiving sCS systemic corticosteroid therapy for 6-14 days. In 56.5% of patients with TAB temporal artery biopsy -positive results (35 of 62), MR imaging displayed symmetrical and simultaneous inflammation of arterial segments. CONCLUSION: MR imaging of superficial cranial arteries is accurate in the initial diagnosis of GCA giant cell arteritis . Sensitivity probably decreases after more than 5 days of sCS systemic corticosteroid therapy; thus, imaging should not be delayed. Clinical trial registration no. DRKS00000594 .


Asunto(s)
Arteritis de Células Gigantes/diagnóstico , Imagen por Resonancia Magnética/métodos , Arterias Temporales/patología , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organometálicos , Estudios Prospectivos , Sensibilidad y Especificidad
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