H Helbig

University Hospital Regensburg, Ratisbon, Bavaria, Germany

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Publications (144)165.72 Total impact

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    ABSTRACT: The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications.
    No preview · Article · Dec 2015 · Annals of Hematology
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    ABSTRACT: Background The majority of patients suffering from chronic health disabilities is beyond 70 years of age. Typical late-onset chronic diseases include those affecting the heart, the kidney, cancer, and conditions of the eye such as age-related macular degeneration. These diseases disable patients for many years and largely compromise autonomy in daily life. Due to challenges in recruiting the elderly, the collection of population-based epidemiological data as a prerequisite to understand associated risk factors and mechanisms is commonly done in the general population within an age-range of 20 to 70 years. Methods/Design We establish the German AugUR study (Age-related diseases: understanding genetic and non-genetic influences - a study at the University of Regensburg), a prospective study in the mobile elderly general population in and around Regensburg in eastern Bavaria. In the long term, we aim to recruit 3,000 persons of Caucasian ethnicity with at least 70 years of age via residents’ registration offices and conduct 3-year follow-ups. The study protocol includes a standardized interview regarding social and life-style factors, medication history, quality-of-life, and existing diagnoses of common diseases. The participants undergo medical examinations for ophthalmological, cardiovascular or diabetes-related conditions, and general measurements of body shape and fitness. The program is particularly tailored for the elderly. Biobanking of whole blood, serum, plasma, and urine is conducted and standard laboratory measurements are performed in fresh samples. Discussion AugUR is specifically designed as a research platform to host studies of late onset diseases. Consequently, this platform will help (1) to unravel the genetic and non-genetic etiology of disease development and progression, (2) to serve as control group of elderly individuals for comparisons with various patient groups, (3) to derive prevalence and incidence data on chronic diseases, and (4) to provide clinical reference parameters for the elderly mobile general population. This data will foster our understanding of disease mechanisms, which may ultimately help to improve prevention, diagnosis, and therapy for frequent chronic diseases. Here we present the baseline study protocol of AugUR.
    Full-text · Article · Oct 2015 · BMC Geriatrics
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    ABSTRACT: Background: We report a 35-year-old female patient with cerebral manifestations of chronic graft-versus-host disease (cGvHD) and putative retinal involvement after allogeneic peripheral blood stem cell transplantation (alloHSCT). Patient and methods: The patient experienced recurrent episodes of fever and encephalitic signs 7 months after alloHSCT during taper of immunosuppression (IS). Results: Cerebral magnetic resonance imaging (MRI) showed non-gadolinium-enhancing confluent periventricular lesions and cerebrospinal fluid inflammation. After exclusion of infectious causes, treatment with steroids and antiepileptics improved cognitive deficits. Steroid reduction provoked a relapse responding to IS. 2 years later, she complained of right-sided blurred vision and floaters; both eyes showed whitish circumscribed retinal infiltrations, cellular infiltration of the vitreous and mild bilateral optic disc edema. Oncological and neurological work-up ruled out infectious diseases and other GvHD manifestations. Symptoms and signs resolved under continued systemic IS, leaving pigmented retinal scars. After IS withdrawal, classical cutaneous cGvHD developed, resolving on systemic IS. 94 months after transplantation, she is doing well. Conclusion: To our knowledge, this is the first observation of retinal involvement of cerebral cGvHD manifestations with retinal infiltrations documented in the absence of other causes and in parallel to periventricular lesions in cerebral MRI. Based on bone marrow histology, we discuss a small vessel pathophysiology of cGvHD.
    No preview · Article · Oct 2015 · Oncology Research and Treatment
  • A M Joussen · Horst Helbig

    No preview · Article · Sep 2015 · Klinische Monatsblätter für Augenheilkunde
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    ABSTRACT: A 69-year-old female patient presented with a therapy-resistant corneal ulcer due to contact lenses, which had been present in the left eye for 1 month. The best corrected visual acuity at the first visit was 0.2. Keratitis with a central corneal ulcer was found. A corneal curettage was performed followed by inpatient therapy with antibiotic eye drops. The first PCR result was negative and the microbiological culture was sterile after 48 h. The clinical findings improved during the hospital stay. There was a decrease in the size of the corneal ulcer and an increase of best corrected visual acuity up to 0.4 so that the patient was discharged. After 8 weeks the patient presented again with a painful eye and visual decline to 0.1. The left eye showed a fulminant keratitis with corneal abscess so that a second course of therapy was initiated. The PCR of the second corneal curettage was positive for Fusarium. Antifungal therapy with natamycin 5 % eye drops (via the international pharmacy) and systemic antifungal therapy with voriconazole (2 × 200 mg) were initiated. Due to personal circumstances the patient rejected corneal transplantation, therefore, local and systemic antifungal outpatient treatment was continued for another 2 months until keratoplasty à chaud of the left eye could be performed. At this time there was a clear reduction of inflammation but a descemetocele developed. The patient was treated with local and systemic antifungal therapy (under control of liver and kindney parameters in blood) for 3 months postoperatively in addition to administration of local and systemic steroids. In cases of therapy-resistant keratitis, a Fusarium keratitis should always be considered. Corneal curettage ahead of therapy is very important. Natamycin 5 % eye drops are the first choice of topical antifungal medication in cases of Fusarium keratitis. Even though intensive local and systemic therapy are performed, patients often require corneal transplantation. Due to a high rate of recurrence a longer local and systemic antifungal therapy is required. In the case described here, there was a clear corneal graft without Fusarium recurrence 1 year after surgery and it is presumed the prolonged antifungal therapy before and after surgery was an important factor for this clinical outcome.
    No preview · Article · Jul 2015 · Der Ophthalmologe
  • J Konrad · R Vogt · H Helbig · I Oberacher-Velten
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    ABSTRACT: Pseudotumor cerebri is an idiopathic increase in intracranial pressure, which commonly affects obese women of fertile age. The diagnostic criteria according to the guidelines of the German Society for Neurology are increased cerebrospinal fluid (CSF) pressure, symptoms of increased CSF pressure, normal results of CSF examination, no relevant medication and a lack of structural and vascular lesions in magnetic resonance imaging (MRI). This article presents the case of a 39-year-old male patient who presented at hospital with visual obscuration and recently occurred double vision. Except for a recently diagnosed thrombosis of the left jugular vein of unknown origin, there was nothing else of note in the medical history. Biomicroscopic examination showed papilledema with hemorrhages and cotton wool spots. The CSF opening pressure was initially > 50 cmH2O. During therapy by lumbar puncture (three times), oral carbonic anhydrase inhibitors and loop diuretics, the abducens nerve palsy and papilledema receded. Anticoagulation therapy (initially with coumarin derivatives, then with low molecular weight heparins) was unsuccessful in eliminating the thrombosis of the jugular vein. Surgical intervention was not recommended by the vascular surgeons. This case report demonstrates the unusual combination of (idiopathic) intracranial hypertension and thrombosis of the jugular vein, which occurred spontaneously and without any detectable coagulation disorders.
    No preview · Article · Mar 2015 · Der Ophthalmologe
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    ABSTRACT: A prematurely born male infant (24+5 gestational weeks, birth weight 485 g) was diagnosed with bilateral aggressive posterior retinopathy of prematurity (AP-ROP) in zone I. After obtaining informed written consent from the parents, one eye was treated with diode laser photocoagulation and the other eye with 0.25 mg intravitreal ranibizumab. Laser photocoagulation was found to be an effective tool for fast regression of AP-ROP; however, medium-term evaluation showed poor macular formation and peripheral retinal detachment. The intravitreal injection led to a slower but better control of the AP-ROP and central foveal reflexes showed better anatomical outcome.
    No preview · Article · Jan 2015 · Der Ophthalmologe

  • No preview · Article · Jan 2015 · Der Ophthalmologe
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    ABSTRACT: Purpose: To describe clinical characteristics of Müller cell sheen dystrophy (MCSD) in two unrelated patients followed for 10 years. Methods: Best-corrected visual acuity (BCVA), kinetic perimetry, biomicroscopy, ophthalmoscopy, fundus photography, fluorescein angiography, fundus autofluorescence, near-infrared reflectance, optical coherence tomography (OCT), and electroretinography (ERG). Results: Case 1: A 61-year-old woman showed internal limiting membrane (ILM) folds at the posterior pole (OU), and cystoid macular edema (CME) in OD. During follow-up, BCVA decreased from 0.2 to 0.06 (OD) and from 0.7 to hand movements (OS). Fundus presented fluctuant CME and subretinal fluid, and an increase in ILM folds and intraretinal schisis cavities. ERG was negative in OD and initially normal in OS. Case 2: A 60-year-old man was first diagnosed with epiretinal membrane before MCSD with ILM folds was detected. OCT showed schisis cavities in all retinal layers. After vitrectomy with ILM peeling in OD because of visual loss and massive CME, BCVA recovered from 0.05 to 0.4. BCVA in OS remained at 0.6. OD developed negative ERG. Conclusions: MCSD presents with late onset, ILM folds, intraretinal schisis cavities, and negative ERG. Visual loss is accompanied by CME and subretinal fluid. Vitrectomy with ILM peeling led to BCVA increase and anatomic improvement.
    No preview · Article · Oct 2014 · Documenta Ophthalmologica

  • No preview · Article · Sep 2014 · Journal of neuroimaging: official journal of the American Society of Neuroimaging
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    ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs) which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV) AMD (hsa-mir-301-3p, pcorrected = 5.6*10−5, hsa-mir-361-5p, pcorrected = 8.0*10−4 and hsa-mir-424-5p, pcorrected = 9.6*10−3). A combined profile of the three miRNAs revealed an area under the curve (AUC) value of 0.727 and was highly associated with NV AMD (p = 1.2*10−8). To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA) were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005). Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.
    Full-text · Article · Sep 2014 · PLoS ONE
  • I M Oberacher-Velten · H Helbig
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    ABSTRACT: Retinal haemorrhages are one of the three cardinal manifestations of the "shaken baby syndrome" or "non-accidental head injury" in childhood. The role of an ophthalmologist in suspected non-accidental head injury has not only medical but also legal aspects and has been discussed controversially in the literature. The differential diagnosis and the specificity of retinal haemorrhages in childhood for an abusive head trauma will be pointed out in this paper.
    No preview · Article · Sep 2014 · Klinische Monatsblätter für Augenheilkunde
  • H Helbig · A Joussen

    No preview · Article · Sep 2014 · Klinische Monatsblätter für Augenheilkunde
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    ABSTRACT: Hintergrund Berichtet wird über einen Fall primärer lokalisierter konjunktivaler AL (λ-Leichtketten)-Amyloidose. Methoden Fallbericht. Ergebnisse Eine 73-jährige Patientin stellte sich mit einer seit 1 Jahr langsam zunehmenden Gewebsvermehrung der Bindehaut des linken Auges vor. Es stellte sich eine gelblich-lachsfarbene diffuse Gewebsmasse in der inferomedialen Conjunctiva bulbi und im unteren Fornix dar. Eine inzisionale Biopsie wurde durchgeführt. Histopathologische und immunhistochemische Untersuchungen ergaben interstitielle und vaskuläre Amyloidablagerungen von λ-Leichtketten. Die Diagnose einer konjunktivalen Amyloidose wurde gestellt. Die systemische Evaluation lieferte keinen offenkundigen Hinweis für eine systemische Amyloidose. Trotzdem wurde aufgrund einer nicht erklärten Herzinsuffizienz in Absprache mit dem niedergelassenen Hämatologen eine probatorische, systemische Chemotherapie mit 3 Zyklen Melphalan und Prednisolon durchgeführt. Sechs Monate später persistierte die konjunktivale Gewebsvermehrung im unteren Fornix, eine vollständige Exzision wurde durchgeführt. Bei den Verlaufskontrollen nach 16, 24 und 44 Monaten bestand kein Hinweis auf ein Rezidiv in der Spaltlampenuntersuchung sowie magnetresonanztomographisch nach 16 und nach 24 Monaten kein Hinweis für kraniale und orbitale Infiltration. Schlussfolgerungen Die konjunktivale λ-Leichtketten (AL)-Amyloidose ist eine seltene klinische Entität. Aufgrund der Heterogenität der Amyloidose hinsichtlich klinischer Präsentation, Muster der amyloidassoziierten Organtoxizität, Verbindung zu lymphoproliferativen Erkrankungen und Rate der Krankheitsprogression ist die Identifizierung der Amyloidablagerungen essenziell, ebenso wie der Ausschluss einer systemischen Beteiligung.
    No preview · Article · Aug 2014 · Der Ophthalmologe
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    ABSTRACT: Purpose: Trabeculectomy is a frequently used surgical procedure in open-angle glaucomas. The present study analyses the outcome and complications after trabeculectomy or re-trabeculectomy depending on the preoperative intraocular pressure (IOP) < 30 mmHg and ≥ 30 mmHg. Methods: One hundred and eighteen patients were included in this retrospective study. Primary ocular outcomes were the postoperative IOP at discharge and postoperative complications such as choroidal detachment and flattening of the anterior chamber. The necessity of postoperative interventions such as needle revisions, viscoelastic injections or surgical revision was documented. Results: In this survey 118 patients (68 men, 50 women) were included (age [arithmetic mean] 68.3 ± 12.1 years). The postoperative follow-up period was 6-9 months. In 60 patients the preoperative IOP was < 30 mmHg, in 58 patients ≥ 30 mmHg. Postoperative complications were flattening of the anterior chamber (< 2 corneal thickness) in 11 patients (9.3 %) and temporary choroidal detachment in 20 patients (16.9 %). On the day of discharge the mean IOP was 9.8 mmHg. Hence the IOP was on average reduced by 17 mmHg (SD 11.2 mmHg). Postoperative interventions were necessary in 28 patients (23.7 %). Seventeen (14.4 %) developed tenon cysts which were treated by needle revision of the bleb. Nine patients (7.6 %) underwent a viscoelastic injection for persistent hypotony and 10 patients underwent bleb revision (8.5 %). Conclusions: This study does not show statistically significant differences depending on preoperative IOP in temporary choroidal detachment and postoperative interventions. A postoperative flattening of the anterior chamber was found statistically significantly more often in patients with higher preoperative IOP.
    No preview · Article · Jun 2014 · Klinische Monatsblätter für Augenheilkunde
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    ABSTRACT: Induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) has widely been appreciated as a promising tool to model human ocular disease emanating from primary RPE pathology. Here, we describe the successful reprogramming of adult human dermal fibroblasts to iPSCs and their differentiation to pure expandable RPE cells with structural and functional features characteristic for native RPE. Fibroblast cultures were established from skin biopsy material and subsequently reprogrammed following polycistronic lentiviral transduction with OCT4, SOX2, KLF4 and L-Myc. Fibroblast-derived iPSCs showed typical morphology, chromosomal integrity and a distinctive stem cell marker profile. Subsequent differentiation resulted in expandable pigmented hexagonal RPE cells. The cells revealed stable RNA expression of mature RPE markers RPE65, RLBP and BEST1. Immunolabelling verified localisation of BEST1 at the basolateral plasma membrane, and scanning electron microscopy showed typical microvilli at the apical side of iPSC-derived RPE cells. Transepithelial resistance was maintained at high levels during cell culture indicating functional formation of tight junctions. Secretion capacity was demonstrated for VEGF-A. Feeding of porcine photoreceptor outer segments revealed the proper ability of these cells for phagocytosis. IPSC-derived RPE cells largely maintained these properties after cryopreservation. Together, our study underlines that adult dermal fibroblasts can serve as a valuable resource for iPSC-derived RPE with characteristics highly reminiscent of true RPE cells. This will allow its broad application to establish cellular models for RPE-related human diseases. Electronic supplementary material The online version of this article (doi:10.1007/s12017-014-8308-8) contains supplementary material, which is available to authorized users.
    Full-text · Article · May 2014 · Neuromolecular medicine
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    ABSTRACT: Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
    No preview · Article · Apr 2014 · Bone marrow transplantation
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    ABSTRACT: Ocular color-coded duplex sonography (OCCS), when performed within the safety limits of diagnostic ultrasonography, is an easy noninvasive technique with high potential for diagnosis and therapy in diseases with raised intracranial pressure and vascular diseases affecting the eye. Despite the capabilities of modern ultrasound systems and its scientific validation, OCCS has not gained widespread use in neurological practice. In this review, the authors describe the technique and main parameter settings of OCCS systems to reduce potential risks as thermal or cavitational effects for sensitive orbital structures. Applications of OCCS are the determination of intracranial pressure in emergency medicine, and follow-up evaluations of idiopathic intracranial hypertension and ventricular shunting by measuring the optic nerve sheath diameter. A diameter of 5.7 - 6.0 mm corresponds well with symptomatically increased intracranial pressure (> 20 cmH2O). OCCS also helps to discriminate between different etiologies of central retinal artery occlusion - by visualization of a "spot sign" and Doppler flow analysis of the central retinal artery - and aids the differential diagnosis of papilledema. At the end perspectives are illustrated that combine established ultrasound methods such as transcranial color-coded sonography with OCCS.
    No preview · Article · Mar 2014 · Ultraschall in der Medizin
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    ABSTRACT: BACKGROUND AND PURPOSECentral retinal artery occlusion (CRAO) is most often indirectly diagnosed by lack of retinal perfusion. Direct embolus characterization may help to understand the natural course and low response to treatment. In a previous study we identified a hyperechoic signal within the optic nerve and in the central retinal artery (“spot sign”).METHODS In this study we performed a follow-up investigation in 7 patients with CRAO and positive spot sign indicating the embolic cause of the occlusion after a median interval of 17 months (range 11-38 months) using a battery of tests (ocular color-coded sonography, optic coherence tomography [OCT], fundoscopy, amongst others).RESULTSThe spot sign persisted in all patients, none had high-grade internal carotid artery stenosis, stroke or transient ischemic attacks. Four patients were completely blind, 3 patients were able to recognize hand movements. OCT demonstrated retinal atrophy, and fundoscopy revealed only minimal arterial perfusion.CONCLUSIONS The hyperechoic spot sign may be an important predictive prognostic marker for persistent loss of vision. Its persistence may indicate calcified or cholesterol emboli and may explain the low therapeutic success rate to thrombolysis. Further studies on their origin and significance in atherosclerotic disease are warranted.
    Full-text · Article · Mar 2014 · Journal of neuroimaging: official journal of the American Society of Neuroimaging
  • F Lehmann · T Jenisch · H Helbig · M A Gamulescu
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    ABSTRACT: There are some reports showing isolated cases of drusen regression after pars plana vitrectomy (ppV) with peeling of the internal limiting membrane (iLM). Drusen characteristics after iLM peeling was investigated in this study. The data of 527 patients who had received iLM peeling between 2004 and 2012 were retrospectively collected and those patients with retinal drusen were selected for the study. Fundus photographs before and after vitrectomy due to a macular hole or epiretinal gliosis were compared and drusen arrangement in the peeling site was analyzed. The aim of the study was to show whether there was drusen regression 2-5 months after surgery. Out of the 527 patients 11 showed central macular drusen, 4 with confluent large drusen (> 63 µm diameter) and 7 with small hard drusen (≤ 63 µm diameter). One patient showed drusen regression after iLM peeling without any changes in the other eye and all other patients showed no differences in the drusen findings (n = 6) or even some additional drusen (n = 4) without drusen alterations in the other eye. The results of this study could not confirm some reports showing drusen regression after iLM peeling in the peeling site in general and there was only one single case of central drusen regression.
    No preview · Article · Feb 2014 · Der Ophthalmologe

Publication Stats

661 Citations
165.72 Total Impact Points


  • 2008-2015
    • University Hospital Regensburg
      • Klinik für Augenheilkunde
      Ratisbon, Bavaria, Germany
  • 2007-2015
    • Universität Regensburg
      • Department of Ophthalmology
      Ratisbon, Bavaria, Germany
  • 2012
    • Inselspital, Universitätsspital Bern
      Berna, Bern, Switzerland
  • 2011
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2005
    • University of Zurich
      • Ophthalmology Unit
      Zürich, Zurich, Switzerland
  • 2000-2005
    • Kantonsspital St. Gallen
      San Gallo, Saint Gallen, Switzerland
  • 2003
    • Cantonal Hospital of Schwyz
      Schwyz, Schwyz, Switzerland