Crystalline deposits in the cornea and various areas of the kidney as symptoms of an underlying monoclonal gammopathy: a case report.

BACKGROUND: Plasma cell dyscrasias (PCD) are characterized by an abnormal production of intact monoclonal immunoglobulins or parts such as heavy or light chains. In most cases, the monoclonal protein (also termed paraprotein) is produced by a clonal plasma cell population. The production of monoclonal proteins can result in deposits of various types and localization depending on the type, amount, and electrochemical properties of the paraprotein. One histopathologic presentation, albeit rare, are crystalline deposits. They can form in various organs and hence cause a wide spectrum of symptoms. CASE PRESENTATION: A 49-year-old man presented to the emergency department with eyestrain and foreign body sensation after overhead drilling. Examination of the eyes revealed crystalline deposits in the cornea of both eyes. After additional diagnostic testing, deposits were attributed to free light chains. Monoclonal gammopathy of undetermined significance (MGUS) was diagnosed according to serum electrophoresis and immunofixation. Four years later, new onset of proteinuria was detected. A percutaneous biopsy of the kidney showed severe light chain podocytopathy with secondary focal segmental glomerulosclerosis (FSGS) and light chain proximal tubulopathy (LCPT). In these lesions, crystalline deposits identical to the corneal deposits were found in ultrastructural and immunofluorescent analysis. The patient was diagnosed with monoclonal gammopathy of renal significance (MGRS), and a plasma cell directed therapy was initiated. CONCLUSIONS: PCD can present with a wide array of symptoms and are notoriously difficult to diagnose. Extrarenal manifestations such as crystalline deposits in the cornea are one possible manifestation. The case presented herein emphasizes the notion that extrarenal paraprotein deposits warrant a thorough search for the underlying clonal disease.

[Treatment of vascularized high-risk eyes with a Boston keratoprosthesis]. / Versorgung von vaskularisierten Hochrisikoaugen mittels Boston-Keratoprothese.

BACKGROUND: In severely compromised and vascularized high-risk eyes, the Boston keratoprosthesis procedure is often the last treatment option. The transparency of the optics is not impaired by endothelial immune reactions. METHODS: This review article discusses relevant literature as well as our own data and experiences with the Boston keratoprosthesis in high-risk eyes. The relevant complications as well as the postoperative management are discussed. RESULTS: In more than 60% of the high-risk eyes a long-term increase in visual acuity can be achieved. Keratoprosthesis retention rates show a variable span with reported mean 5­year retention rates of 75%. The most common postoperative complications include the formation of a retroprosthetic membrane and keratolysis in up to 50% each. More than 70% of the eyes already suffer from (secondary) glaucoma preoperatively, so that glaucoma surgery is performed simultaneously in at least 20% of cases and in the postoperative course further antiglaucomatous surgery is necessary in up to 31%. Vitreoretinal complications include, in particular, sterile vitritis and infectious endophthalmitis but persistent hypotonia is also described in one third of patients. CONCLUSION: The Boston keratoprosthesis is an alternative to conventional corneal replacement if the prognosis for allogeneic transplants is poor. Postoperative complications are common; therefore, postoperative management plays an important role. For vascularized high-risk eyes, however, it is often the only remaining option for visual rehabilitation.

Eye changes in space : New insights into clinical aspects, pathogenesis, and prevention.

BACKGROUND: More than ever research into changes in the eye caused by long-term space flight is becoming the focus of the international and national space agencies National Aeronautics and Space Administration (NASA), European Space Agency (ESA) and German Aerospace Center (DLR). In addition to space radiation-induced cataract formation considerable eye changes, summarized under space flight-associated neuro-ocular syndrome (SANS), can occur. OBJECTIVE: This article gives an overview of the current state of research and future directions in the field of research concerned with ocular alterations in SANS and presents the relevance for terrestrial ophthalmological research. MATERIAL AND METHODS: An analysis of existing publications on SANS in PubMed and reports on the risk of SANS published by the NASA of the USA was carried out. RESULTS: The reasons for the development of the eye changes in space have not been clarified. Factors such as the increase in intracranial pressure, fluid shifts, hypercapnia and genetic factors are the subject of intensive research efforts. A terrestrial model for the induction of papilledema could be established (bed rest studies with -6° head-down tilt as a space analogue). Countermeasures for the development of eye changes, such as intermittent artificial gravity, are the subject of current research studies. CONCLUSION: Research into SANS as part of bed rest studies will provide further important insights in the future for space research and also for terrestrial research. Clinical research projects can be derived from space research.

[Eye changes in space : New insights into clinical aspects, pathogenesis and prevention]. / Augenveränderungen im All : Aktuelles zu Klinik, Pathogenese und Prävention.

BACKGROUND: More than ever research into changes in the eye caused by long-term space flight is becoming the focus of the international and national space agencies National Aeronautics and Space Administration (NASA), European Space Agency (ESA) and German Aerospace Center (DLR). In addition to space radiation-induced cataract formation considerable eye changes, summarized under space flight-associated neuro-ocular syndrome (SANS), can occur. OBJECTIVE: This article gives an overview of the current state of research and future directions in the field of research concerned with ocular alterations in SANS and presents the relevance for terrestrial ophthalmological research. MATERIAL AND METHODS: An analysis of existing publications on SANS in PubMed and reports on the risk of SANS published by the NASA of the USA was carried out. RESULTS: The reasons for the development of the eye changes in space have not been clarified. Factors such as the increase in intracranial pressure, fluid shifts, hypercapnia and genetic factors are the subject of intensive research efforts. A terrestrial model for the induction of papilledema could be established (bed rest studies with -6° head-down tilt as a space analogue). Countermeasures for the development of eye changes, such as intermittent artificial gravity, are the subject of current research studies. CONCLUSION: Research into SANS as part of bed rest studies will provide further important insights in the future for space research and also for terrestrial research. Clinical research projects can be derived from space research.

Bruch's membrane opening-based optical coherence tomography of the optic nerve head: a useful diagnostic tool to detect glaucoma in macrodiscs.

PurposeTo compare Bruch's membrane opening (BMO)-based spectral domain optical coherence tomography (SD-OCT) and margin based confocal scanning laser tomography (CSLT) of the optic nerve head (ONH) to visual field function in large optic discs (macrodiscs) and to assess performance for glaucoma detection.MethodsIn a case-control, cross-sectional study, 125 eyes of 125 patients with disc size >2.45 mm2, thereof 44 glaucoma and 11 ocular hypertension (OHT) patients and 70 healthy controls underwent SD-OCT and CSLT examination, visual field testing and clinical evaluation. Mean outcome measures BMO-based minimum rim width (BMO-MRW), retinal nerve fiber layer thickness (RNFLT) in SD-OCT, and rim area measured in CSLT were compared and correlated to visual field function.ResultsAll participants had a mean disc area of 2.91±0.38 mm2 in CSLT and a BMO area of 2.45±0.39 mm2 (r=0.76;P<0.001). In glaucoma patients, visual field mean deviation was -10.0±6.1 dB. Global BMO-MRW correlated better to visual field function (Spearman's Rho (ρ)=0.71; P<0.001) than RNFLT (ρ=0.52;P<0.001) and CSLT rim area (ρ=0.63; P<0.001). BMO-MRW was significantly decreased with higher visual field loss (P<0.001). In ROC analysis, diagnostic power to differentiate glaucoma patients and healthy controls was highest for BMO-MRW (Area under curve, AUC=0.96; sensitivity at 95% specificity=82%). Rim area in CSLT (AUC=0.91; sensitivity=61.0%; P=0.04) and RNFLT (AUC=0.89; sensitivity=61%; P=0.01) were significantly less powerful.ConclusionsIn macrodiscs, BMO-MRW has the best diagnostic power to discriminate glaucoma patients from normal controls compared to RNFLT and rim area in CSLT. Additionally, BMO-MRW seems to reflect the structure-function relationship better than the other two parameters.

[Indications for Retinal Laser Therapy Revisited]. / Wann wird heute noch gelasert?

BACKGROUND: Laser therapy is an important treatment option in retinal diseases, especially in cases of vascular involvement. Most approaches are based on coagulation of retinal structures. As there is increasing use of agents targetting vascular endothelial growth factor in the treatment of macular diseases, indications for the use of laser treatment need to be reviewed carefully, especially with respect to their significance in first line therapy. This article explains recent strategies and treatment protocols. MATERIALS AND METHODS: Review of current literature in PubMed as well as synopsis of relevant guidelines. RESULTS AND CONCLUSION: Retinal laser therapy is still widely used within retinal opthalmology and covers a large spectrum of indications. Despite the success of medical approaches, retinal laser therapy remains an indispensable treatment option for proliferative diabetic retinopathy, central or peripheral vein occlusion and less frequent pathologies, such as retinopathy of prematurity or Coats's disease.

[Boston keratoprosthesis: 73 eyes from Germany : An overview of experiences from two centers]. / Boston-Keratoprothese: 73 Augen aus Deutschland : Übersicht der Erfahrungen aus zwei Zentren.

BACKGROUND: The Boston Keratoprosthesis (B-KPro) is a therapeutic option for corneal replacement for visual rehabilitation in eyes with poor a prognosis for penetrating keratoplasty (high-risk eyes). Since 2009, this approach has been used in the MVZ Prof. Neuhann, Munich, and since 2013 also at the Department of Ophthalmology, University of Cologne. An overview of results from the first 73 eyes in these departments is presented. METHODS: All recipient eyes of both centers which received a B-KPro type I (BI-KPro) between November 2009 and March 2017 were included. Indications, preoperative findings, intraoperative procedures, and clinical results, as well as postoperative complication and retention rates were documented and analyzed. RESULTS: A total of 73 eyes from 68 patients (mean age 55 ± 21.1 years, range 7 months-93 years; 26 women, 42 men) were treated with a BI-KPro. In 53 eyes (72.6%) the BI-KPro was implanted due to corneal graft failure, whereas BI-KPro was used as the primary corneal replacement in 20 eyes (27.4%). In 46 eyes (63.0%) a long-term increase in visual acuity was achieved and in 21.9% visual acuity was stabilized, while a decrease in preoperative visual acuity occurred in 15.1% of cases. During an average follow-up of 24.7 ± 23.0 months (range 1-78 months), 1.7 ± 2.4 re-interventions (range 0-9) were required. Only 4 keratoprostheses (5.5%) could not be retained. In 3 eyes (4.2%), a change of the BI-KPro device was necessary. CONCLUSION: There is a wide range of indications for BI-KPro in eyes with a poor prognosis for conventional keratoplasty. The surgical technique is safe but with a notable postoperative complication rate, which does not seem to decrease in the medium or long term. The retention rate is excellent for eyes without stem cell deficiency. Nevertheless, the BI-KPro is the only therapeutic option for high-risk eyes and leads to a gain in visual acuity in most cases.

[Deep Anterior Lamellar Keratoplasty : Experiences and results of the first 100 consecutive DALK from the University Eye Hospital of Cologne]. / Tiefe anteriore lamelläre Keratoplastik : Erfahrungen und Ergebnisse der ersten 100 konsekutiven DALK aus der Kölner Universitätsaugenklinik.

BACKGROUND: Deep anterior lamellar keratoplasty (DALK) is a treatment option for patients with diseases of the corneal stroma without endothelial involvement and has been used at the Department of Ophthalmology of the University of Cologne since July 2011. Experiences and results of the first 100 consecutive cases from Cologne with a minimum follow-up of 1 year are summarized. MATERIALS AND METHODS: We included the first 100 consecutive DALKs. Indications for anterior lamellar keratoplasty, the feasibility of the surgery, the postoperative course, in addition to the complications and clinical outcome 3 months after complete suture removal, were examined. The rate of conversion to penetrating keratoplasty in all planned DALKs during the observation period was also recorded. Mean follow-up was 25.6 ± 13 months. RESULTS: In 99 eyes of 97 patients (72 men, 25 women; aged 43.5 ± 16.9 years), the first 100 DALKs were performed in the period between 26 July 2011 and 27 January 2015 (87 cases electively, 13 cases as DALK à chaud, 1 of which was a second DALK). The most common indications were keratoconus (68%), corneal ulcers (13%), and corneal scarring (13%). On average, visual acuity increased from 0.83 ± 0.4 to 0.09 ± 0.1 logMAR. In 6 eyes (6%) grafts could not be preserved because of a corneal ulcer (n = 5, n = 3 of which were recurrent episodes), and in 1 case because of postoperative bulbus trauma. Rate of conversion to penetrating keratoplasty during the observation period was 11.5%. In eyes with keratoconus, visual acuity increased from 0.89 ± 0.4 before DALK to 0.06 ± 0.1 logMAR (best-corrected with contact lens) and the conversion rate was 17.6%. CONCLUSION: DALK represents a reliable technique for corneal transplantation in different pathological conditions of the cornea and the risk of endothelial immune responses can be avoided completely. In keratoconus and corneal scarring in particular, DALK can be used as a safe treatment option with very good results.

[Proliferative Vitreoretinopathy: Therapeutic Strategies]. / Proliferative Vitreoretinopathie: therapeutische Strategien.

BACKGROUND: Development of proliferative vitreoretinopathy (PVR) is one of the most important complications of vitreoretinal surgery. Reaching the decision to treat and surgical treatment itself are both challenging. MATERIALS AND METHODS: Our own data and a review of the literature in PubMed are summarised. RESULTS: Pharmacological approaches to the prevention and treatment of proliferative vitreoretinopathy have been limited to concepts that have been investigated in preclinical and a few clinical studies. Anti-inflammatory and antiproliferative substances may be mentioned in this context. Surgical techniques range from scleral buckling to the gold standard pars plana vitrectomy, preferably with silicone oil endotamponade. Applying an encircling band, retinotomy or retinectomy can be useful in reattaching the tractional shortened retina. CONCLUSION: Surgery is still the method of choice for the treatment of PVR. Pharmacological strategies to prevent or treat PVR have not been established.

[Corneal donation : Dilemma between growing demand and declining donor rate]. / Hornhautspende : Ein Dilemma zwischen wachsender Nachfrage und sinkender Spenderrate.

BACKGROUND: One of the most important requirements for successful corneal transplantation is the availability of donor tissue and thus the approval for postmortem corneal tissue donation. The aim of this study was to investigate donor willingness compared to the continuously increasing demand in recent years. MATERIAL AND METHODS: Archives of the local eye bank at the Department of Ophthalmology, University of Cologne, Germany in the time period between 1 July 2011 and 31 December 2015 were examined regarding the willingness for corneal donations in deceased patients from the University Hospital of Cologne. Absolute numbers of deceased, exclusion criteria for donation as well as the rate of negative and affirmative decisions were evaluated. RESULTS: In 235 (5.1 %) out of 4593 deceased at the University Hospital of Cologne, corneal donation was accomplished during the observation period. Of the patients 2923 (63.6 %) were excluded because of absolute contraindications for corneal donation and the rate of absolute contraindications increased from 46.6 % in 2011 to 68.9 % in 2015. Willingness for corneal donation in potentially suitable deceased patients diminished from 34.9 % in 2011, to 34.3 % in 2012, 35.5 % in 2013, 28.4 % in 2014 and to 24.1 % in 2015. In relation to the total number of deceased, the number of corneal tissue donations decreased from 11.5 % in 2011 to 3.5 % in 2015. CONCLUSION: Despite a rising demand, data from Cologne seem to indicate that the number of corneal donations has declined to some extent. In order to increase the number of corneal donors in the future, further educational work as well as standardization and optimization of the tissue donation process seem to be urgently needed.

Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

In vitro stimulation with a non-peptidic alkylphosphate expands cells expressing Vgamma2-Jgamma1.2/Vdelta2 T-cell receptors.

The majority of peripheral blood gammadelta T cells in healthy adult humans express the Vgamma2/Vdelta2 T-cell receptor (TCR) and generate TCR-mediated, major histocompatibility complex (MHC)-unrestricted proliferative responses to low molecular weight alkylphosphates. Vgamma2/Vdelta2 populations after antigen proliferation maintained diversity in the CDR3s of Vgamma2 mRNA, indicating that the response was polyclonal or oligoclonal, and were enriched for Vgamma2 TCR chains containing the Jgamma1.2 segment. Alkylphosphate stimulation further skewed an already biased peripheral blood gammadelta T-cell population and increased the abundance of Vgamma2-Jgamma1.2/Vdelta2 T cell receptors, suggesting similarities between the alkylphosphate response and peripheral selection mechanisms shaping this repertoire in human beings.

V gamma 2 TCR repertoire overlap in different anatomical compartments of healthy, unrelated rhesus macaques.

Gammadelta T cells show preferential homing that is characterized by biased TCR repertoire at different anatomical locations. The processes that regulate this compartmentalization are largely unknown. A model that allows repeated multiple sample procurement under different conditions and enables with relatively straightforward extrapolation to a human situation will facilitate our understanding. The peripheral blood Vgamma2 T cell population is the best-characterized human gammadelta T cell subset. To determine its diversity at multiple immunocompartments matching blood, colon, and vagina samples from rhesus macaques were investigated. Four joining segments used in Vgamma2-Jgamma transcripts were identified, including one segment with no human counterpart. Like in humans, the rhesus peripheral blood Vgamma2 TCR repertoire was limited and contained common sequences that were shared by genetically heterogeneous animals. Furthermore, this subset comprised several phylogenetically conserved Vgamma2 complementarity-determining region 3 (CDR3) motifs between rhesus and humans. Common sequences were also found within the colon and vagina of the same animal, and within the peripheral blood and intestine of different unrelated animals. These results validate rhesus macaques as a useful model for gammadelta TCR repertoire and homing studies. Moreover, they provide evidence that the concept of limited but overlapping Vgamma TCR repertoire between unrelated individuals can be extended including the mucosa of the digestive and reproductive tract.

Impact of Haemophilus influenzae type b (Hib) conjugate vaccines on Haemophilus influenzae meningitis in Wisconsin.

The first effective Haemophilus influenzae type b (Hib) conjugate vaccines were approved for use in children and infants between 1987 and 1990. In 1993, the federal government began the Childhood Immunization Initiative (CII), a program to improve the rate of vaccination of children nationwide. Subsequently, the proportion of 19 to 35-month-old children who received three or more doses of Hib vaccine rapidly increased from 28% in 1992 to 90% by 1995, with a concurrent dramatic decline in the incidence of H. influenzae meningitis. We reviewed cases of H. influenzae meningitis reported to the Wisconsin Division of Public Health from 1981 to 1997. The mean annual incidence of H. influenzae meningitis declined 96% from 2.4 cases per 100,000 persons in the pre-vaccination period (1981-1986) to less than 0.1 case per 100,000 persons after Wisconsin had achieved 90% Hib vaccination coverage (1994-1997). H. influenzae meningitis occurrence declined dramatically among all age groups, including 96% among children aged less than 1 year old, 99% among 1-4 and 5-9 year olds, and 46% among persons 10 or more years old. Consistent with national trends, the majority of H. influenzae meningitis cases reported in 1997 was caused by non-type b strains of H. influenzae.

Surface Behavior of Spread Sodium Eicosanyl Sulfate Monolayers.

The surface behavior of spread sodium eicosanyl sulfate monolayers is characterized by determining the dilational moduli from different pi/A isotherms and from surface stress relaxation experiments in the short-time range (<10 min). The elasticities derived from the pi/A isotherms differ depending on the experimental conditions. The quasi-equilibrium isotherm displays a plateau in the range of coexistence of the condensed and the expanded phases and strong increases caused by the formation of a solid-like phase. In contrast, nonequilibrium pi/A isotherms yield effective elasticities showing a maximum within the phase coexistence range. The formation of a solid phase cannot be detected because of the onset of monolayer collapse. Different stress relaxation experiments were carried out for monolayer compression and dilation using transient drop volume jumps. Depending on the experimental run, these experiments lead to consistent and complementary results with those derived from pi/A isotherms under comparable conditions. The stress recoveries yield a relaxation time, a dilation viscosity, and a parameter characterizing the homogeneity of the relaxation process. The stress relaxation is interpreted accounting for both the nonequilibrium between the monolayer and the bulk phase and the nonequilibrium within the monolayer. The influence of alkylsulfate hydrolysis on the presented results was checked. It was found that within the time scale of the experiments no influence of hydrolysis could be detected. Copyright 1998 Academic Press.

[Otogenic brain abscess and middle ear cancer]. / Otogener Hirnabszess und Mittelohrkarzinom.

An uncommon case is reported in which both a brain abscess and a carcinoma of the middle ear were diagnosed at the same time. Before the histology was known, a cholesteatoma was thought to be the cause of the brain abscess. The difficulties in the differential diagnosis are discussed.

Interlaboratory survey on thallium in urine.

Quality assurance of analytic results was legalized in the Federal Republic of Germany by the law regulating the calibration of measuring devices of July 11, 1969, and the ordinance concerning the exception from compulsory calibration dated June 29, 1970. Accordingly, in the field of health care the Guidelines of the Medical Society of West Germany for the realization of quality assurance activities have to be followed. Since January 1, 1974, the law regulating the calibration of measuring devices has been fully effective. In the field of legal medicine the clinico-toxicologic analysis is considered to be a part of health care. As far as quantitative determinations are considered, these analyses have to follow the regulations mentioned above. To fulfil the basic program, adequate control samples are necessary. For toxicologic analysis there have been no control samples so far. Therefore, a control sample for thallium has been developed which can be used for long- and short-term interlaboratory surveys. The results are reported.