K U Loeffler

University of Bonn, Bonn, North Rhine-Westphalia, Germany

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Publications (91)137.52 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A 65-year-old patient presented with increasing loss of vision in the right eye. A relative afferent pupillary defect as well as visual field perimetry deficits in an otherwise unremarkable eye led to the presumed diagnosis of ischemia of the optic nerve; however, further imaging revealed an extensive necrotic bronchial carcinoma in the left upper lobe metastasizing to the orbit with compression of the optic nerve. The clinical and histological features are discussed with respect to possible primary origins of orbital metastases.
    Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 12/2014;
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    ABSTRACT: Abstract Objectives: We report anterior segment abnormalities in both eyes of a 33 week old fetus endorsing the diagnosis of MIDAS syndrome (acronym for microphthalmia, dermal aplasia, and sclerocornea). Methods: After abortion the fetus was examined by a standard pediatric autopsy including macroscopic and microscopic examination of both eyes. Principal results: Post mortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears), and an agenesis of the corpus callosum. An array-CGH revealed a deletion of the short arm of X chromosome (region Xp22.2 to p22.32). Ophthalmopathological examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. Conclusion: General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report underlines that the ophthalmopathological investigation of fetal eyes can be of great value for the further classification of syndromes.
  • Martina C Herwig, Frank G Holz, Karin U Loeffler
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    ABSTRACT: ABSTRACT Purpose: The aim of this article is to investigate whether macrophages show a proliferative activity (as indicated by Ki67 expression) and their distribution at the site of inflammation. Materials and Methods: Six different macrophage-containing lesions from six different patients (four females, two males; age range: 16-58 years) were stained for macrophage markers (CD68, CD163) and Ki67 by immunohistochemistry. Immunofluorescence techniques were used to investigate dual-labeling of the specimens for CD68, CD163 and Ki67, respectively. Results: With immunofluorescence staining, scattered cells in all specimens were dual-labeled for CD68-Ki67 and CD163-Ki67. All lesions were composed of mixed infiltrates of M1 (CD68+CD163-) and M2 (CD68+CD163+) macrophages. The center of epithelioid-cell granulomas and foreign body giant cells was exclusively composed of M1 macrophages. Conclusions: This study shows that CD68+ and CD163+ cells express Ki67, a marker for proliferative activity at the site of inflammation. Until recently, macrophages were regarded as end-differentiated cells without mitotic activity. Since self-renewal of M1 and M2 macrophages has been described in the literature, staining of macrophages with Ki67 may indicate proliferative activity or at least an activation state. The distribution of macrophages in classic granulomatous lesions with only M1 macrophages in the avascular center represents an immune response to foreign body material, whereas the proangiogenic M2 macrophages are located mostly in the surrounding inflammatory tissue and seem to be mandatory for the vascularization of the inflammatory tissue.
    Current eye research. 08/2014;
  • M C Herwig, K U Löffler
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    ABSTRACT: The investigation of foetal eyes not only allows for the observation of ocular development. It is supportive and sometimes even mandatory for the diagnosis of systemic and ocular syndromes. This review gives an overview about the investigation of foetal eyes, their assignment to developmental stages, challenges related to the investigation of foetal eyes, clinically relevant syndromes, and academic questions. The morphological development of the eye has been investigated since the 19th century and will not be covered in this article. The investigation of foetal eyes that have been collected during the routine paediatric autopsy, is complicated by artifacts. Artifacts are the result of autolysis, fixation, and mechanical manipulation. They have to be distinguished from genuine findings. Besides the search for findings such as coloboma or cataract, the morphological classification of the foetal eye is of importance. The anterior-posterior diameter allows for the diagnosis of microphthalmia. The case reports comprise Goldenhar's syndrome, MIDAS syndrome and others. In conclusion, the investigation of foetal eyes is often helpful and critical for paediatric diagnostics and should be performed with great care.
    Klinische Monatsblätter für Augenheilkunde 07/2014; 231(7):720-8. · 0.70 Impact Factor
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    ABSTRACT: During human ocular development, expression of proteins varies in different maturation stages. This study aims to characterize structures in human fetal eyes stained by the lymphatic marker podoplanin (D2-40) with emphasis on the stage of maturation and the presence of intraocular lymphatic structures. Formalin-fixed paraffin-embedded eyes from 40 human fetuses between 10 to 38 weeks of gestation (WoG) were investigated. Immunohistochemical stains were performed for D2-40, LYVE-1 as a secondory lymphatic marker, and CD34 as a control for endothelial reactivity. A semiquantitative analysis of antigen expression in different segments of the eye was performed by light microscopy. The intensity of antigen expression was graded with a score ranging from 0 to 3. Podoplanin expression was found with a variable intensity in 97.5% of the eyes, in particular in lymphatic vessels of the conjunctiva (n=26), conjunctival and corneal epithelium (n=33), corneal endothelium (n=4), trabecular meshwork (n=28), and optic nerve sheaths (n=23). A slight, equivocal staining reaction was noted in the choroid (n=14). There was a correlation of antigen reactivity and the gestational age for corneal endothelial reactivity in earlier gestational stages (p=0.003) and trabecular meshwork in older eyes (p=0.031). D2-40 positive Müller cells were detected in two eyes ≥ 32 WoG. Thus, aside from conjunctival lymphatic vessels, podoplanin was expressed in several structures of the human fetal eye and the ocular adnexae at different gestational stages. Podoplanin positive structures were also found in the choroid and the chamber angle. However, lymphatic vessels or its progenitors could not be unequivocally identified in intraocular structures during 10-38 weeks of gestation. There is no evidence from our data that transient intraocular lymphactics develop in the fetal eye between 10-38 weeks of gestation.
    Experimental Eye Research 01/2014; · 3.03 Impact Factor
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    ABSTRACT: Evaluation of the lens, including cataractous changes, is often of paramount importance in the classification of fetal syndromes or forensic questions. On histology, the crystalline lens is - especially in fetal and infant eyes - an organ susceptible to numerous artifacts. Thus, the aim of our study was to study various factors (including fixatives) that might have an impact on lens histomorphology. Twenty eyes from ten fetuses (formalin fixation: n = 10, glutaraldehyde fixation: n = 10), matched for gestational age and abortion (spontaneous vs. induced), were investigated macroscopically and by light microscopy. Sections were stained with routine hematoxylin & eosin (H&E), and periodic acid schiff (PAS). The age of the fetal eyes ranged from 15 to 36 weeks of gestation. Lens artifacts were analyzed and compared to fetal and adult lenses with definitive cataractous changes. In addition, 34 eyes from 27 fetuses with trisomy 21 were investigated for lens changes. All lenses showed artifacts of varying extent, in particular globules, vacuoles, clefts, anterior/posterior capsular separation, subcapsular proteinaceous material, fragmentation of the lens capsule/epithelium, and a posterior umbilication. Glutaraldehyde-fixed lenses displayed less artifacts compared to those fixed in formalin. Slight differences in the appearance of artifacts were found dependent on the fixative (formaldehyde vs glutaraldehyde) and the kind of abortion (iatrogenous vs spontaneous). The gestational age did not have a significant influence on the type and extent of lens artifacts. The lenses from fetuses with trisomy 21 displayed similar lens artifacts with no specific findings. Alterations in fetal lens morphology are extremely frequent and variable. These artifacts have to be carefully taken into account when interpreting post-mortem findings. Thus, the postmortem diagnosis of a fetal cataract should be made with great caution, and should include, in adherence to our proposed diagnostic flow diagram, the macroscopic lens assessment. Reference slides with a proven cataract are recommended for comparison in equivocal cases.
    Albrecht von Graæes Archiv für Ophthalmologie 11/2013; · 1.93 Impact Factor
  • Dr. T. Heeren, F.G. Holz, K.U. Löffler
    Der Ophthalmologe 11/2013; · 0.53 Impact Factor
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    ABSTRACT: A 24-year-old female patient was admitted to hospital with a deep stromal corneal defect on the right eye and a melting marginal keratitis on the left eye with a differential diagnosis of Mooren's ulcer. Despite intensive topical and systemic therapy, the ulcer perforated 3 days later and perforating keratoplasty à chaud was performed. The histological examination of the cornea showed a mainly intact corneal structure with a sharp demarcation line between the melting process close to the limbus and the unaffected tissue. The limbal area was interspersed with inflammatory cells. During the subsequent clinical course, despite intensive immunosuppressive therapy with Cellcept, systemic and local cyclosporin and methotrexate the left eye perforated and was subsequently treated by perforating keratoplasty. Under immunosuppression with methotrexate and local steroids no recurrence or progression has occurred so far.
    Der Ophthalmologe 09/2013; · 0.53 Impact Factor
  • Der Ophthalmologe 09/2013; · 0.53 Impact Factor
  • Acta ophthalmologica 08/2013; · 2.44 Impact Factor
  • T Heeren, F G Holz, K U Löffler
    Der Ophthalmologe 06/2013; · 0.53 Impact Factor
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    ABSTRACT: Purpose: To study the corneal development in the human fetal eye with particular emphasis on the epithelial basement membrane and Bowman's layer. Thus, immunohistochemical markers supposed to stain this region were employed. Material and Methods: 19 formalin-fixed fetal eyes and a 16-day-old newborn's cornea without any obvious irregularities of the anterior segment were investigated. The age of the fetal eyes ranged from 11 to 38 week of gestation (WoG). The eyes (including the corneal thickness) were measured and, in addition to routine hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, immunohistochemical labeling with antibodies to collagen IV, V, IX, and XVII was performed. Results: Analysis of the H&E stains revealed that measurements of corneal thickness correlated well with corneal development as a basic indicator for maturation. In a more detailed immunohistochemical analysis, collagen IV was expressed in the epithelial basement membrane (BM) of the cornea, conjunctiva, and Descemet's membrane in fetal eyes up to the age of 23 WoG. In fetal eyes older than 23 WoG, staining was confined to the limbal area only. With the antibody against collagen V, the corneal stroma and the BM were intensely stained. Bowman's layer (first detected at 17 WoG by light microscopy) was not labeled. Anti-collagen IX labeled predominantly the conjunctival and corneal epithelium. With anti-collagen XVII, the BM of the cornea and conjunctiva was stained in all fetal eyes, whereas intracellular expression in the epithelium increased with age. Conclusion: Our results indicate maturation-associated variations of collagen expression in the human cornea. Measurements of the corneal thickness may serve as an additional parameter to narrow down the developmental age with possible implications for pediatric pathology and forensic issues.
    Current eye research 11/2012; · 1.51 Impact Factor
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    ABSTRACT: Diseases of the posterior compartment and the orbit are characterised by histological findings, most of which can be reproduced clinically. Examples are the examination of calcifications in retinoblastoma by ultrasonography. In the present review, histological findings of tumour and other diseases of the posterior ocular compartment and the orbit are presented and correlated with the clinical pictures and imaging techniques: uveal melanoma, choroidal nevus, choroidal metastases, choroidal hemangioma, retinoblastoma, Coat's disease, sympathetic ophthalmia, pleomorphic adenoma (benign mixed tumour) of the lacrimal gland, dacryoadenitis, lymphoma, rhabdomyosarcoma, Langerhans cell histiocytosis, orbital metastases, and phthisical eyes. Histopathology is usually the gold standard for a definitive diagnosis. It is very important for residents and those in training to become familiar with clinico-pathological correlations as these provide insight in pathophysiological processes. Regarding ophthalmic surgery, ophthalmic pathology offers the possibility to study wound healing and complications. A close collaboration between clinicians and ocular pathologists allows for an optimised processing of the submitted tissue and diagnosis. Thus, pre- and postoperative care can also be improved. This outstanding knowledge that ophthalmologists have gained over the last decades and beyond, should be preserved and passed on to the next generations in order to maintain a high standard in ophthalmological care.
    Klinische Monatsblätter für Augenheilkunde 07/2012; 229(7):705-15. · 0.70 Impact Factor
  • K M Zilkens, N Bastian, K U Löffler, F G Holz
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    ABSTRACT: Tarantulas have urticating hairs which may cause severe irritation of the skin, respiratory tract and eyes. Inflammation and granulomas (ophthalmia nodosa) can develop in the anterior and posterior segment of the eye presenting as keratoconjunctivitis or uveitis. We present a case of a female patient with an intracorneal tarantula hair and subsequent keratouveitis after contact with a pet tarantula. Because of the unsatisfactory effects of topical steroids surgical removal of the tarantula hair was performed which resulted in remission of the inflammatory signs and recovery of visual acuity.
    Der Ophthalmologe 06/2012; 109(8):798-800. · 0.53 Impact Factor
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    ABSTRACT: PURPOSE: To present light and electron microscopic as well as immunohistochemical findings after corneal cross-linking (CXL). METHODS: Six keratoconus corneas after CXL, 12 keratoconus corneas without CXL, and 7 normal corneas were examined by light microscopy, indirect immunohistochemistry using antibodies against proapoptotic BAX, antiapoptotic survivin, and BCL-2, and anti-smooth muscle actin and, in part, by transmission electron microscopy. Direct immunofluorescence with 4'6-diamidino-2-phenylindole was performed to analyze keratocytes/area in the anterior, middle, posterior, peripheral, and central corneal stroma. RESULTS: The period between CXL and keratoplasty ranged from 5 to 30 months. All keratoconus corneas showed the typical histological changes. Increased proapoptotic BAX expression and/or antiapoptotic survivin expression were noticed in keratocytes and endothelium in 2 keratoconus specimens after CXL. Smooth muscle actin was only observed in subepithelial scar tissue of 2 keratoconus corneas without CXL. Keratoconus corneas after CXL revealed a significant reduction in keratocyte counts in the entire cornea (P = 0.003) compared with keratoconus corneas without CXL and normal corneas. This difference was because of a loss of keratocytes in the anterior (P = 0.014) and middle (P = 0.024) corneal stroma. Keratocytes in CXL corneas were reduced in the center (P = 0.028) and the periphery (P = 0.047). CONCLUSIONS: CXL in human keratoconus can cause considerable morphologic corneal changes up to 30 months postoperatively. Especially noteworthy is a long-lasting, maybe permanent, keratocyte loss in the anterior and middle corneal stroma involving the central and peripheral cornea. As long-term corneal damage after CXL is of genuine concern, particular care should be taken to perform this procedure only in accordance with investigational protocols.
    Cornea 05/2012; · 1.75 Impact Factor
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    ABSTRACT: A 63-year-old patient presented with a small painless nodular tumour of his left lower eyelid which had increased in size over the last few weeks. The tumour was excised by wedge resection and submitted for ophthalmopathologic examination. Histopathologic examination revealed a cystic lesion of apocrine origin with focal proliferations. The proliferative cells appeared pleomorphic and displayed marked atypia. Staining with Ki67 revealed a significant mitotic activity supporting the diagnosis of an apocrine adenocarcinoma of Moll. As the lesion displayed in most parts characteristics of a benign apocrine hidrocystoma, a thorough and critical histopathological examination is required in such cases to avoid missing an early malignant transformation.
    Case reports in pathology. 01/2012; 2012:471368.
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    Acta ophthalmologica 11/2011; 90(4):e331-2. · 2.44 Impact Factor
  • The British journal of ophthalmology 10/2011; 95(10):1470, 1478. · 2.92 Impact Factor
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    Acta ophthalmologica 06/2011; 90(2):e155-156. · 2.44 Impact Factor
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    ABSTRACT: Purpose To investigate the earliest histological changes of the retina after laser treatment of diabetic retinopathy by using Spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Heidelberg, Germany). Methods This study examined 320 laser burns from 16 eyes of 12 patients with early severe non-proliferative diabetic retinopathy (NPDR) that underwent laser photocoagulation according to the protocol which the Early Treatment Diabetic Retinopathy Study (ETDRS) recommended. SD-OCT scan was performed before the laser treatment, then 1 hour, 24 hours, 48 hours, 72 hours and 1 week after treatment. The main outcome measure was thickness change in outer retina (OR) in the region localized to the laser treatment. Results The alterations of retinal thickness at the location of the laser burns mainly occurred within the retinal layers that expand from the outer plexiform layer (OPL) to the outer highly reflective layer (HRL) (IS/OS). From 1 hour to 48 hours after laser treatment, the thickness of retina, from OPL to the HRL, increased with time. At 48 hours post- treatment, the increase of retinal thickness from OPL to the HRL reached a peak. At 72 hours, the thickness of retina from the OPL to the HRL began to decrease as a result of the outward migration of OPL towards the retinal pigment epithelial (RPE). At 1 week post- treatment, hyporeflectivity at the level of IS/OS and RPE atrophy was observed in the areas corresponding with the laser burns; the thickness of retina from the OPL to the HRL was essentially within normal thickness. Conclusions This study demonstrates the subtle in vivo imaging changes of laser lesion and the trend of earliest changes in the thickness of the retina in the level of OPL-HRL, first increasing then subsequently decreasing as shown by SD-OCT in DR post laser treatment.
    Albrecht von Graæes Archiv für Ophthalmologie 04/2011; 250(3):473. · 1.93 Impact Factor

Publication Stats

354 Citations
137.52 Total Impact Points


  • 2002–2014
    • University of Bonn
      • Institutes of Molecular Medicine and Experimental Immunology
      Bonn, North Rhine-Westphalia, Germany
  • 2012
    • Marienhospital Aachen
      Aachen, North Rhine-Westphalia, Germany
  • 2011
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 2006–2009
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
  • 1989–1998
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1992–1995
    • University of Illinois at Chicago
      • Department of Ophthalmology and Visual Sciences (Chicago)
      Chicago, IL, United States