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Purpose Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. Materials and Methods In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18 – 87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). Results DES occurred with significantly (p Conclusion Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.

Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The etiology and pathogenesis is multifactorial, multifaceted and not yet fully understood. The present work should provide deeper insights into possible triggering factors and correlating comorbidities.In German ophthalmological practices 306 persons (174 women, 132 men, age: 18-87 years) were interviewed by questionnaire regarding concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the Chi-square test (SPSS statistical software).DES occurred with a significantly (p0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidemia, hyperuricemia, osteoporosis and nephrolithiasis.Some of the known comorbidities and DES-risk factors, e.g. computer work or depression were confirmed. In contrast, the higher prevalence of hyperlipidemia, hyperuricemia, osteoporosis, nephrolithiasis, and fibroids among DES-patients was described for the first time in this work. Causal connections between DES and certain comorbidities should constitute the subject of further investigation in the future. Zusammenfassung Zielsetzung: Das Trockene Auge (TA) ist eine der häufigsten Erkrankungen der Augenoberfläche. Betroffene leiden unter verschiedenen subjektiven Beschwerden, die die Lebensqualität mitunter stark beeinträchtigen. Die Ätiologie und Pathogenese sind multifaktoriell, vielschichtig und noch nicht vollständig geklärt. Die vorliegende Arbeit soll tiefere Einblicke in mögliche auslösende Faktoren und korrelierende Komorbiditäten geben.In deutschen Augenarztpraxen wurden 306 Personen (174 Frauen, 132 Männer, Alter: 18-87 Jahre) per Fragebogen zu Begleiterkrankungen und möglichen weiteren auslösenden Faktoren befragt. In 170 Fällen wurde ein TA durch einen Augenarzt diagnostiziert. Die statistische Vergleichsanalyse zwischen Personen mit und ohne TA wurde mit dem Chi-Quadrat-Test (Statistiksoftware SPSS) durchgeführt. Ergebnisse: TA traten signifikant (p0,05) häufiger bei Frauen über 40 Jahren auf sowie bei Personen, die Bildschirmarbeit und Klimaanlagen ausgesetzt waren, bei Personen mit chronischen Augenentzündungen, Myomen (Hysterektomie), trockener Haut, arterieller Hypertonie, die medikamentös behandelt werden musste, Herzrhythmusstörungen, Fettleber, Magengeschwür, Blinddarmentzündung, Cholezystektomie, Depression, Hyperlipidämie, Hyperurikämie, Osteoporose und Nephrolithiasis. Schlussfolgerung: Einige der bekannten Komorbiditäten und TA-Risikofaktoren, z. B. Bildschirmarbeit oder Depression, wurden bestätigt. Die höhere Prävalenz von Hyperlipidämie, Hyperurikämie, Osteoporose, Nephrolithiasis und Myomen bei TA-Patientinnen wurde dagegen in dieser Arbeit erstmals beschrieben. Kausale Zusammenhänge zwischen TA und bestimmten Komorbiditäten sollten in Zukunft Gegenstand weiterer Untersuchungen sein.

PURPOSE: To assess patient satisfaction and quality of life after refractive lens exchange with a trifocal intraocular lens (IOL). METHODS: Consecutive patients who underwent refractive lens exchange with the AT LISA tri or AT LISA tri toric IOL (Carl Zeiss Meditec AG) at one of five surgical centers were surveyed for their quality of life and satisfaction after surgery using a standardized questionnaire. Patient responses were compared to patient characteristics such as age, sex, axial lengths, and preoperative refraction. RESULTS: A total of 102 patients with 204 treated eyes were included in the analysis. The mean age was 54.6 ± 5.2 years. A total of 172 eyes were hypermetropic, 3 were emmetropic, and 25 were myopic, with a mean preoperative refractive error of 0.93 ± 2.17 diopters. Reported postoperative satisfaction was as follows: 81.4% stated that their expectations were completely met and 17.6% stated that they were partially met. Self-reported refractive error quality of life improved significantly in all queried areas of life. Most frequently reported postoperative limitations were driving at night and driving in bad weather conditions. Halos were reported by 91 (90.1%) patients. CONCLUSIONS: Patient satisfaction and self-reported quality of life after refractive lens exchange with the AT LISA tri or AT LISA tri toric IOL was high. Glare and halos remain the only significant drawback of the procedure, leading to 40% of patients experiencing difficulties in night driving. Preoperative communication of these drawbacks is obligatory to avoid postoperative disappointment. [ J Refract Surg . 2021;37(11):768–774.]

Background While therapeutic success of the limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in vitro expanded allogeneic ABCB5+ LSCs derived from human cadaveric limbal tissue. Methods We developed and validated a Good Manufacturing Practice- and European Pharmacopeia-conform production and quality-control process, by which ABCB5+ LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population, and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells’ engraftment potential, biodistribution behavior, and safety. Results ABCB5+ LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food & Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD. Conclusion Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5+ LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient’s LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.

Aim To evaluate major complications after intravitreal injection of dexamethasone implants (Ozurdex) and their clinical management. Methods In a retrospective observational study between 2014 and 2016 at two university hospitals, we reviewed the clinical records of 1241 consecutive macular edema patients treated with the dexamethasone implant, and separated severe adverse events in the injection procedure from those that were post-injection complications. We evaluated the cause and the outcomes in each case. Results In twenty-one procedures (1.69%) we noticed significant complications during and after intravitreal injection of the dexamethasone implant. Complications related to the injection procedure were in one case, that a second implant was injected by mistake in the same eye on the same day. In another case, the implant lodged in the sclera during retraction of the injector needle. Leaking scleral tunnel at the injection site led to hypotony in another case. There were 10 cases of post-injection displacement of the implant into the anterior chamber and one case with a migrated and trapped device between the intraocular lens and an artificial iris. Displacement typically occurred in patients with preexisting risk factors: eyes with complicated intraocular lens implantation, iris reconstruction or iris defects or pseudophakic eyes after vitrectomy were prone to develop this complication. Displacement led to secondary corneal decompensation with pseudohypopyon. One case developed an endophthalmitis, and we observed four cases of retinal detachment. Two eyes presented with long-lasting hypotony due to ciliary insufficiency. Conclusion Treatment with the dexamethasone implant may cause various expected or unexpected complications that may have serious consequences for the patient and require further surgery. To reduce complications, clinicians should evaluate certain risk factors before scheduling patients for dexamethasone implant treatment and use proper injection techniques.

To quantify and compare the amounts of surfactant proteins SP-A, SP-B, SP-C and SP-D in the tear fluid collected from patients with dry eye syndrome and from individuals with a healthy ocular surface.Schirmer strips were used to collect tear fluid from both eyes of 241 volunteers (99 men, 142 women; age range: 18-87 years). Dry eye syndrome was diagnosed by ophthalmologists in 125 patients, whereas the healthy control group comprised 116 individuals. The total protein concentration was determined via Bradford assay. The relative concentration of surfactant proteins SP-A through -D was measured by enzyme-linked immuno-sorbent assay (ELISA).The mean relative concentrations of SP-A, SP-C and SP-D were significantly higher in the dry eye group as compared to the healthy controls (p0.05, one-way ANOVA). SP-B was also detected at a higher concentration in the dry eye group, but the difference to the control group was not statistically significant.The upregulation of SP-A and SP-D in the dry eye group is probably related to these proteins' known antimicrobial and immunomodulatory effects at the ocular surface. It may represent a pathophysiological response to the inflammatory condition of the ocular surface in dry eye. The upregulation of SP-B and SP-C may represent an effort of the lacrimal system to reduce surface tension and thus to counteract the increased tendency of the tear film to tear in dry eye.

Purpose To evaluate the repeatability and comparability of biometry parameters between a Scheimpflug-based topography with axial length measurement (Pentacam AXL, Oculus, Wetzlar, Germany) and a swept-source optical biometry (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany). Methods A total of 50 eyes from 50 adult subjects had biometry measurements in one session three times using the Pentacam AXL and the IOLMaster 700. Keratometry, anterior chamber depth (ACD) and axial length (AL) values were obtained by both devices. Mean keratometry (Kmean) was calculated and the corneal spherocylinder was converted into power vectors (J0, J45). Repeatability was assessed based on intraclass correlation coefficient (ICC). Agreement was evaluated by linear regression analysis and Bland–Altman analysis by calculating the mean difference and 95% limits of agreement (LoA). Results Assessment of intraoperator repeatability by means of ICC showed excellent reproducibility of measurements for both devices and all parameters examined ranging from 0.994 to 1.0. IOLMaster 700 exhibited significantly higher Kmean (p Conclusions Both devices provide high reproducible values for all parameters investigated. J0 and J45 values are statistically and clinically interchangeable between Pentacam AXL and IOLMaster 700. All other parameters are statistically different. In clinical practice, the differences for ACD and AL are to small and the values can be used interchangeable. However, Kmean values are clinically and statistically different and cannot be used interchangeable between the two devices.

Neuronatin (NNAT) is a proteolipid involved in cation homeostasis especially in the developing brain. Its expression has been associated with the progression of lung cancer, glioblastoma, and neuroblastoma as well as glucose induced apoptosis in pancreatic cells. We performed a retrospective study of 148 breast cancer specimens for NNAT expression by immunohistochemistry to evaluate this protein as a prognostic marker for breast cancer. We found a high NNAT immunoreactivity score (by multivariate cox regression) to be an independent prognostic marker for relapse-free (hazard ratio HR = 3.55, p = 0.002) and overall survival (HR = 6.29, p

Impaired corneal healing is still a major cause of blindness. As RAGE (receptor for advanced glycation endproducts) is involved in inflammation and wound healing in other tissues, we here investigated its relevance for corneal wound healing. Corneal re-epithelialization after alkaline injury was analysed in an ex-vivo approach with cultured, enucleated eyes from mice either of the C57Bl/6 NChR genotype (RAGE+/+) and mice of the same strain lacking the RAGE gene (RAGE-/-). The wound area was determined time dependently by fluorescence imaging using fluorescein staining. The eyes of RAGE-/- mice showed a significantly slower re-epithelialization than eyes of the RAGE+/- and the RAGE+/+ genotype. In immunohistochemistry, RAGE expression was increased in wounded corneas whereas the abundance of the RAGE ligand HMGB1 was unaffected, but an increase in S100b-like proteins was revealed upon injury. However, neither the addition of the RAGE agonist HMGB1 or an HMGB1 antagonising antibody nor bovine S100b protein to the culture medium of the wounded eyes had an effect on corneal wound closure in ex-vivo. Further gene expression analysis by RT-PCR demonstrated an increase in RAGE expression on the mRNA level, no significant regulation of HMGB1 and a differential regulation of the S100 gene family after alkaline burn of the cornea. In conclusion, RAGE is clearly involved in corneal re-epithelialization most probably mediated by signalling via S100 proteins.

Ophthalmologists and interventional radiologists are not the only professionals for whom diseases of the efferent tear duct system occupy centre stage; this applies also to ENT specialists involving endonasal conservative or surgical treatment. On the basis of current knowledge and taking account of results yielded by own research in recent years and of clinical aspects, we here give an overview of basic knowledge on the anatomy and physiology of the nasolacrimal system. In doing so functional aspects regarding tear transport as well as embryological and pathophysiological issues are integrated.

Hintergrund: Anhand der klinischen und histopathologischen Befunde von 2 Patienten mit traumatischer Avulsio bulbi werden die zugrunde liegenden Pathomechanismen und potenziellen Verletzungsfolgen diskutiert. Anamnese und Befund: Beide Patienten erlitten im alkoholisierten Zustand einen Fahrradunfall mit Eindringen des Bremshebels in die Orbita. Hierdurch kam es zu einem Abriss des Sehnervs und einer Verlagerung des Bulbus vor die Lidspalte. Therapie und Verlauf: Bei einem Patienten gelang es intraoperativ, den Bulbus in die Orbita zu reponieren, wahrend das Auge des anderen Patienten enukleiert werden musste. Funktionell resultierten ein vollstandiger Funktionsverlust des betroffenen Auges sowie ein Gesichtsfeldausfall mit Visusminderung des Partnerauges bei einem der beiden Patienten. Schlussfolgerung: Die Avulsio bulbi stellt ein schwerwiegendes Krankheitsbild dar, dem haufig Freizeit- und Verkehrsunfalle zugrunde liegen. Neben der primaren Wundversorgung ist insbesondere auf mogliche Funktionsausfalle am nicht unmittelbar in das Unfallgeschehen einbezogenen Auge zu achten.

Background Laboratory analysis and optical quality assessment of explanted hydrophilic intraocular lenses (IOLs) with clinically significant opacification after posterior lamellar keratoplasty (DMEK and DSAEK). Methods Thirteen opacified IOLs after posterior lamellar keratoplasty, 8 after descemet stripping automated endothelial keratoplasty (DSAEK), 3 after descemet membrane endothelial keratoplasty (DMEK) and 2 after both DSAEK and DMEK were analysed in our laboratory. Analyses included optical bench assessment for optical quality, light microscopy, scanning electron microscopy (SEM) and energy dispersive X-Ray spectroscopy (EDS). Results In all IOLs the opacification was caused by a thin layer of calciumphosphate that had accumulated underneath the anterior optical surface of the IOLs in the area spared by the pupil/anterior capsulorhexis. The calcifications lead to a significant deterioration of the modulation transfer function across all spatial frequencies of the affected IOLs. Conclusions The instillation of exogenous material such as air or gas into the anterior chamber increases the risk for opacification of hydrophilic IOLs irrespective of the manufacturer or the exact composition of the hydrophilic lens material. It is recommended to avoid the use of hydrophilic acrylic IOLs in patients with endothelial dystrophy that will likely require procedures involving the intracameral instillation of air or gas, such as DMEK or DS(A)EK.

Precious little is known about useful functionalization strategies of antibodies that will not impair either reactivity or specificity of this valuable reagent. We used an experimental approach to demonstrate our own experience with published protocols. The conjugates obtained were then tested with regard to their performance against commercially available detection kits. Our results are then viewed in light of published precedence to highlight areas where future effort is needed to refine such versatile tools.

Purpose The purpose of this study was to develop novel therapeutic approaches for the management and treatment of microbial keratitides, especially pathologies resulting from Acantamoeba castellanii inoculations. Methods Growth inhibitory effects of plasma-induced reactive species on cultures of Staphylococcus aureus, Pseudomonas aeruginosa, Acantamoeba castellanii, and MRSA were assayed for in in an in-vitro setting. Human donor corneas were inoculated and cultured with cultures of above pathogens, followed by staining of cells and microscopic analysis. Results Our results show a substantial inhibitory effect of plasma-induced reactive species on the growth and migration of the pathogens tested. Conclusions The effects observed provide foundation for the development of new avenues for the management and therapy of microbial keratitides.

The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites. SFTA3: a novel lung protein with putative protective and immunological functions during inflammation in lung diseases

Endochondral ossification is a process that also occurs in the skeleton of the larynx. Differences in the ossification mechanism in comparison to growth plates are not understood until now. To get deeper insights into this process, human thyroid cartilage was investigated by the use of X-rays and a series of light-microscopic stainings. A statistical analysis of mineralization was done by scanning areas of mineralized cartilage and of ossification. We detected a special mode of endochondral ossification which differs from the processes in growth plates. Thyroid cartilage ossifies very slowly and in a gender-specific manner. Compared with age-matched women, bone formation in thyroid cartilage of men is significantly higher in the age group 41-60 years. Endochondral ossification is prepared by internal changes of extracellular matrix leading to areas of asbestoid fibers with ingrowing cartilage canals. In contrast to growth plates, bone is deposited on large areas of mineralized cartilage, which appear at the rims of cartilage canals. Furthermore, primary parallel fibered bone was observed which was deposited on woven bone. The predominant bone type is cancellous bone with trabeculae, whereas compact bone with Haversian systems was seldom found. Trabeculae contain a great number of reversal and arresting lines meaning that the former were often reconstructed and that bone formation was arrested and resumed again with advancing age. It is hypothesized that throughout life trabeculae of ossified thyroid cartilage undergo adaptation to different loads due to the use of voice.

Advanced glycation end products (AGEs) accumulate as a result of high concentrations of reactive aldehydes, oxidative stress, and insufficient degradation of glycated proteins. AGEs are therefore accepted biomarkers for aging, diabetes, and several degenerative diseases. Due to the Warburg effect and increased oxidative stress, cancer cells frequently accumulate significant amounts of AGEs. As the accumulation of AGEs may reflect the metabolic state and receptor signaling, we evaluated the potential prognostic and predictive value of this biomarker. We used immunohistochemistry to determine the AGE Ne-carboxymethyl lysine (CML) in 213 mammary carcinoma samples and Western blotting to detect AGEs in cell cultures. Whereas no significant correlation between hormone receptor status and CML was observed in cell lines, CML accumulation in tumors was positively correlated with the presence of estrogen receptor alpha, the postmenopausal state, and age. A negative correlation was found for grade III carcinomas and triple-negative cases. In a retrospective Kaplan–Meier survival analysis, there was a statistical trend that high CML accumulation correlated with a more favorable prognosis (relapse-free survival, RFS) under tamoxifen treatment (p = 0.1). In estrogen receptor-negative cases, the high CML content was significantly correlated with an unfavorable outcome (RFS) of chemotherapy (p = 0.046). CML is a therefore a potentially predictive marker for the treatment of breast cancer patients with tamoxifen or chemotherapy.

Objectives/methods The aim of this study was to verify the formation of hydroxyl radicals (·OH) after ultraviolet A (UVA) irradiation of riboflavin (RF) by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and electron spin resonance spectroscopy. Results We found that ·OH were generated via hydrogen peroxide (H(2)O(2)) formation during UVA irradiation of RF. The ·OH radicals were trapped with DMPO yielding 2-hydroxy-5,5-dimethyl-1-pyrroline-N-oxide (·DMPO-OH). The formed radical adduct (·DMPO-OH) accumulated in the RF solution. Argon equilibration of the RF solution completely blocked the formation of the ·DMPO-OH adduct whereas subsequent aeration restored radical adduct generation. The presence of catalase inhibited ·DMPO-OH generation whereas BSA had no influence on ·DMPO-OH formation. Stopping UVA irradiation led to decay of radical adducts. UVA irradiation of H(2)O(2) in the presence of DMPO but without RF also induced the formation of ·DMPO-OH adduct. When adding DMPO to an already irradiated RF solution significantly less ·DMPO-OH was formed during further irradiation. Ultraviolet-visible spectroscopy and high-performance liquid chromatography analysis of RF indicated that RF decayed during UVA irradiation. Discussion The formation of ·OH during UVA irradiation of RF may be part of the oxygen-dependent mechanism involved in the cross-linking therapy of collagen in corneal stroma.

The forkhead transcription factor Foxk1 is an important regulator of myogenic progenitor cells. Since our previous data from mouse retina revealed that Foxk1 is upregulated in Ptf1a-deficient mice we investigated the spatial and temporal expression of Foxk1 during development of mouse retina. Expression of Foxk1 was analyzed on both mRNA and protein level. To identify Foxk1 transcripts, retina and cerebrum (positive control) of adult animals (postnatal day 90 (P90)) was subjected to reverse transcription polymerase chain reaction (RT-PCR) and sequencing of the amplified cDNA. The Foxk1 protein was analyzed in adult retina by Western blotting and in developing eyes at embryonic day (E) 13, 15, E17, P0, P4, P7, P10 and P90 by immunohistochemistry. Localization of Foxk1 expression was determined using cell-specific markers by double labelling. Foxk1 transcripts were detected in adult retina by RT-PCR and confirmed by sequencing. Western blot analysis confirmed the expression of Foxk1 protein in the adult retina. Immunohistochemical examination of developing eyes localized the protein to bipolar, amacrine and ganglion cells with an onset of Foxk1 expression from E15 onwards. The expression pattern during development suggests that Foxk1 may have an important role in retinal cells.

a b s t r a c t Purpose: The aim of this study was to compare central corneal thickness (CCT) between corneas of normal healthy eyes (cNHE), corneas of eyes that had undergone cataract surgery by clear corneal phacoemul- sification with implantation of an intracapsular intraocular lens (cIOL), corneal grafts after penetrating keratoplasty (gPK) and corneas of long-term soft contact lens wearers (cCL). Methods: The study design was a consecutive cross-sectional trial. CCT was measured using rotating Scheimpflug camera (Pentacam, software version 1.16r04) in 80 cNHE, 79 cIOL, 46 gPK and 78 cCL. Anal- ysis of variance (one-way ANOVA) was performed to compare differences of mean values between these four groups. Pearson's or Spearman's correlation coefficient (r) was determined between CCT value and age, follow up time after penetrating keratoplasty (timePK) or contact lens wearing time (timeCL). Results: Means of CCT measurements were comparable between cNHE (mean CCT ± standard deviation, 554 ± 36 m), cIOL (551 ± 40 m) and gPK (534 ± 52 m) as determined by one-way ANOVA. Mean CCT values in cCL (537 ± 37 m) were statistically significantly lower in comparison to cNHE (p = 0.026, 95% CI = 1.43-31.44). There was no linear correlation between age and CCT values of cNHE and cIOL (p = 0.841, r = −0.031 and p = 0.931, r = 0.011, respectively). No linear relationship was determined between CCT values of cCL and timeCL (p = 0.315, r = −0.125). CCT values of gPK did not correlate with timePK (p = 0.738, r = 0.054). Conclusions: The data reported here indicate that in the same statistical model among CCT values of cNHE, cIOL and gPK only long-term soft contact lenses (CL) wearer have significantly lower CCT measurements.

Background: Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that com- promise quality of life. The aim of the study was to find out when patients consult ophthalmolo- gists in Germany and what symptoms they

The present study aims at determining whether enzymes of urea synthesis are expressed in the human lacrimal gland and in tissues of ocular surface (conjunctiva, cornea), to give evidence for the hypothesis that urea can be locally formed from ocular tissues and is important for the composition of the tear fluid. The presences of enzymes (arginase 1, 2 and agmatinase) that directly contribute to the formation of urea were investigated in the lacrimal gland and tissues of ocular surface by RT-PCR and immunohistochemistry. We collected tear fluid, aqueous humour, and blood samples from a total of 38 subjects, and tear fluid samples from a total of 78 subjects, with and without dry-eye syndrome (DES, keratoconjunctivitis sicca), and determined the urea concentration. The enzymes arginase 1, 2 and agmatinase were expressed in all tissues examined except for arginase 1, which was not expressed in the cornea. There was no correlation of urea concentration in tear fluid with aqueous humour and blood plasma (r = 0.13, p = 0.58 and r = 0.45, p = 0.05 respectively). However, correlation of urea concentration between aqueous humour and blood plasma was highly significant (r = 0.7, p = 0.0001). The concentration of urea in the tear fluid of patients with DES compared to healthy control group was significantly reduced (p

Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis. We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 (relaxin/insulin-like family peptide receptor 2) at the ocular surface and in tears. Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface and lacrimal apparatus; in human corneal (HCE), conjunctival (HCjE), and sebaceous (SC) epithelial cell lines; and in human tears by RT-PCR and ELISA. We investigated effects of human recombinant INSL3 (hrINSL3) on cell proliferation and cell migration and the influence of hrINSL3 on the expression of MMP2, -9, and -13 and TIMP1 and -2 was quantified by real-time PCR and ELISA in HCE, HCjE, and SC cells. We used a C57BL/6 mouse corneal defect model to elucidate the effect of topical application of hrINSL3 on corneal wound healing. INSL3 and RXFP2 transcripts and INSL3 protein were detected in all tissues and cell lines investigated. Significantly higher concentrations of INSL3 were detected in tears from male vs. female volunteers. Stimulation of HCE, HCjE, and SC with hrINSL3 significantly increased cell proliferation in HCjE and SC and migration of HCjE. Treatment with hrINSL3 for 24 hours regulated MMP2, TIMP1, and TIMP2 expression. The local application of hrINSL3 onto denuded corneal surface resulted in significantly accelerated corneal wound healing in mice. These findings suggest a novel and gender-specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis and determined a novel role for hrINSL3 in corneal wound healing.

Complex midfacial trauma requires interdisciplinary management. A wide range of reconstructive procedures are needed and if necessary secondary and even tertiary interventions should be performed at the appropriate time. We present the case of a 45-year-old man who was involved in a car accident and presented with severe injuries to the periorbital soft tissue. The focus was on the reconstruction of this sensitive region with regard to functional and aesthetic aspects. In view of the severity of the injuries the final clinical status is considered to be very important. Special issues and pitfalls in the reconstruction of trauma cases and potential management are discussed.

Backround The nasal mucosa is characterized by a multirow high prismatic ciliated epithelium representing the first barrier of the immune defense system against microbial and other environmental pathogenic influences. A number of nonspecific defense mechanisms, including the presence of lactoferrin, peroxidases, proteases, interferons, and lysozymes in nasal secretions, act to counter inflammatory processes. The surfactant proteins (SPs) known from the lungs are important components of the innate immune system. They also influence the rheology of fluids and reduce the surface tension of gas–fluid interphases. The objective of this study was to investigate the protein expression of all four SPs. A specific aim was detection and characterization of SP-C, which had previously not been confirmed in human nasal mucosa. Methods The expression of mRNA for SP-A, -B, -C and -D was investigated using reverse transcriptase polymerase chain reaction on samples of both healthy nasal mucosa and nasal mucosa altered by inflammatory processes (allergic rhinitis and chronic rhinosinusitis). The distribution of all four proteins was determined with monoclonal antibodies using Western blot analysis as well as immunohistochemical methods. Results The results show that all four SPs, including SP-C not detected before this, are nasal mucosa components. A shift was also observed in the expression behavior of the SP-A, -B, and -D in nasal mucosa with inflammatory changes. Conclusion Based on these results, SPs appear to have an important function in immunologic and rheological process of the nasal mucosa and support the prospective therapeutic use of liposomal nasal sprays.

Background Neuronatin (Nnat) was initially identified as a highly expressed gene in neonatal mammalian brain. In this study, we analyze the spatial and temporal expression pattern of Nnat during mouse eye development as well as in the adult. Methods The expression of Nnat was analyzed on mRNA as well as protein level. The presence of Nnat transcripts in the adult retina was examined using reverse transcription-polymerase chain reaction (RT-PCR). Nnat protein expression was evaluated by Western blot and immunohistochemistry during eye development at embryonic day (E) 12, 15, 16 and postnatal day (P) 7, 14, 30 and 175 (adult). Results Immunohistochemical studies of the developing mouse eye revealed Nnat expression in embryonic and adult neuroretina as well as in corneal epithelial, stromal, endothelial cells and in lens epithelium. Expression of Nnat was detected from E12 onwards and was also present in adult eyes. Conclusions The expression pattern suggests that Nnat may play an important role during eye development and in the maintenance of mature eye.

Trefoil factor family (TFF) peptides, and in particular TFF3, are characteristic secretory products of mucous epithelia that promote antiapoptosis, epithelial migration, restitution, and wound healing. For a long time, a receptor for TFF3 had not yet been identified. However, the chemokine receptor CXCR4 has been described as a low affinity receptor for TFF2. Additionally, CXCR7, which is able to heterodimerize with CXCR4, has also been discussed as a potential TFF2 receptor. Since there are distinct structural similarities between the three known TFF peptides, this study evaluated whether CXCR4 and CXCR7 may also act as putative TFF3 receptors.We evaluated the expression of both CXCR4 and CXCR7 in samples of human ocular surface tissues and cell lines, using RT-PCR, immunohistochemistry, and Western blot analysis. Furthermore, we studied possible binding interactions between TFF3 and the receptor proteins in an x-ray structure-based modeling system. Functional studies of TFF3-CXCR4/CXCR7 interaction were accomplished by cell culture-based migration assays, flow cytometry, and evaluation of activation of the mitogen-activated protein (MAP) kinase signaling cascade.We detected both receptors at mRNA and protein level in all analyzed ocular surface tissues, and in lesser amount in ocular surface cell lines. X-ray structure-based modeling revealed CXCR4 and CXCR7 dimers as possible binding partners to TFF3. Cell culture-based assays revealed enhanced cell migration under TFF3 stimulation in a conjunctival epithelial cell line, which was completely suppressed by blocking CXCR4 and/or CXCR7. Flow cytometry showed increased proliferation rates after TFF3 treatment, while blocking both receptors had no effect on this increase. Trefoil factor family 3 also activated the MAP kinase signaling cascade independently from receptor activity.Dimers CXCR4 and CXCR7 are involved in TFF3-dependent activation of cell migration, but not cell proliferation. The ERK1/2 pathway is activated in the process, but not influenced by CXCR4 or CXCR7. These results implicate a dependence of TFF3 activity as to cell migration on the chemokine receptors CXCR4 and CXCR7 at the ocular surface.

Previous studies had shown that donor-specific anti-HLA antibodies may highly influence the survival rate of corneal allografts, although the anterior chamber generally represents an immune-privileged compartment of the eye. We postulated that the introduction of a novel crossmatch procedure for the detection of donor-specific anti-HLA antibodies in recipients awaiting a corneal graft would be adequate to investigate their influence on the outcome of the graft survival. The Antibody Monitoring System (AMS) HLA class I & II crossmatch ELISA was adapted for the use of material from the outer scleral rim instead of blood lymphocytes to isolate the donors' HLA molecules. In case of detectable donor-specific anti-HLA class I and/or class II antibodies (DSA) this result was confirmed using an identification ELISA to specify the detectable recipient's anti-HLA antibodies. PCR-based genetic tissue typing of the donors was performed also using their outer scleral rims. 45 recipients of corneal grafts were analyzed for DSA prior to or after grafting, respectively. 75% of the recipients with preformed DSA exhibited immunological complications up to the complete graft loss in four cases during the first two months. In contrast 77% of the recipients without DSA did not show any complications during the follow up period of averagely 18months. Only two cases of graft loss were observed in this group after 17 and 23months, respectively. The results demonstrate the impact of preventing donor-specific anti-HLA antibodies which are for the first time reliably detectable in any laboratory's daily work using the adapted AMS-ELISA.

The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo. C57BL/6 and C57BL/6 RAGE −/− mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed. The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE −/− mice contained lower levels of the AGE arginine–pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE −/− mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD. These data suggest that RAGE is involved in the development of obesity and insulin resistance.

Purpose To evaluate the influence of somatostatin (SST) and its analog octreotid (Oct) on corneal wound healing processes. Methods The wound healing rate in C57BL/6 mice eyes under SST and Oct treatment was analyzed using an alkali-induced corneal wounding model. Effects of SST and Oct on cell proliferation, migration and quantified protein expression of vascular endothelial growth factor (VEGF) on human corneal epithelial cells (HCE, cell line) were evaluated by means of electric cell-substrate impedance sensing, scratch migration assays and ELISA. ERK1/2 and p38 phosphorylation was investigated by semi-quantitative western blot analysis. Results Ten nanograms per microliters of SST significantly accelerated the wound closure rate of corneal defects in vivo. SST and Oct had no influence on HCE cell proliferation and migration and did not activate ERK1/2 or p38 signaling in HCE cells. However, there was increased VEGF protein expression in cytosolic proteins and medium supernatants of HCE upon Oct stimulation for 24 h. One and 10 ng/ml Oct led to a 2.5-fold and 100 ng/ml Oct to a 4-fold upregulation of VEGF protein expression. Conclusion The data implicate that SST promotes corneal wound healing in a mouse model. However, using a HCE cell line in vitro , the wound healing mechanism does not seem to be supported by proliferation and migration processes or by activation of ERK1/2 and p38 signaling pathways. Other possible mechanisms could be the activation of other pathways and the induction of growth factors such as VEGF that modulate the observed corneal wound healing process.

PURPOSE To assess possible cellular damage in the corneal and conjunctival epithelium after corneal cross-linking treatment. METHODS Riboflavin-dextran solution was applied every 5 minutes to the right eyes of 3 rabbits 10 minutes before and 30 minutes during the irradiation with UVA light of 370 nm and an irradiance of 3 mW/cm at the 8- to 10-o'clock position, including conjunctival, limbal, and central corneal epithelium. In addition, 3 rabbits were treated with UVA light only. The rabbits were killed 24 hours later. The treated eyes were examined histologically using hematoxylin-eosin and periodic acid-Schiff staining, immunohistochemistry, and a terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) apoptosis assay and compared with the left fellow eyes, which served as controls. RESULTS There was no epithelial defect on fluorescein staining. No apoptosis was found in the corneal limbal epithelium, keratocytes, or endothelial cells in the irradiated area. In the adjacent conjunctival epithelium, rare superficial conjunctival epithelial cells were positive in TUNEL staining in all animals. Anti-multicytokeratin-positive staining was demonstrated in both the limbal corneal and the conjunctival epithelium. The proliferation marker Ki-67 was identified in the basal cell layer of the limbal epithelium. The frequency and distribution pattern of goblet cells, multicytokeratin, and the proliferation marker Ki-67 were the same in all eyes compared with the untreated fellow control eyes. CONCLUSIONS Standard corneal cross-linking does not induce significant cellular epithelial damage as assessed by histological methods. Further studies on possible genotoxic and long-term changes would be helpful to complete the risk assessment.

Eine 46-jahrige Patientin berichtete uber Kopfschmerzen, Schwindel und Schleiersehen links seit 4 Tagen sowie Nackenschmerzen seit 1 Jahr. Funduskopisch fand sich links eine abgeblasste und rechts eine zirkular randunscharfe Papille. Auserdem stellten wir eine beidseitige Anosmie fest. Im cMRT stellte sich eine Raumforderung in der vorderen Schadelgrube dar. Es handelte sich um ein endotheliomatoses Meningeom mit WHO-Grad 1. Als Diagnose wurde ein Foster-Kennedy-Syndrom gestellt.

Purpose: To determine whether the epithelium of the human nasolacrimal ducts contains aquaporins (AQPs), a family of membrane proteins that function as selective pores and are able to transport water, glycerol, and other small solutes across the cell plasma membrane. Methods: Expression of AQPs 0 and 1–10 in human nasolacrimal duct tissue was determined by reverse transcription polymerase chain reaction (RT-PCR). Positive PCR amplification products were verified by direct cDNA sequencing. Western blot analysis was used to detect AQPs 3–5. Antisera specific for AQPs were used in immunohistochemical analysis to determine the presence and distribution of ten AQPs (AQP 0 and 1–9) in epithelia and subepithelial glands of the nasolacrimal ducts. All samples investigated originated from human postmortem tissue. Results: In human nasolacrimal duct samples, AQPs 1, 3, 4, 5, 7, 8, 9, and 10 were identified by RTPCR. No RT-PCR products were detected for AQPs 0, 2, and 6. All AQPs, which were detected by RT-PCR, were also confirmed by direct sequencing of the cDNA. Immunohistochemical analyses revealed AQPs 1, 3, 5, 7, 8, and 9 in human nasolacrimal duct epithelium and were detected in different cells. Expression of AQP 4 could not be detected immunohistochemically but by Western blot analysis. Protein detection of AQP 10 could not be performed due to the unavailability of an appropriate antibody. Conclusions: The results suggest specific roles for AQPs in water transport through the epithelium of the nasolacrimal ducts and underline the presumption that tear fluid components are selectively absorbed in the nasolacrimal passage.

Objective Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a member of a family of protease-resistant peptides containing a highly conserved motif with 6 cysteine residues. Recent studies have shown that TFF3 is expressed in injured cornea, where it plays a role in corneal wound healing, but not in healthy cornea. Since cartilage and cornea have similar matrix properties, we undertook the present study to investigate whether TFF3 could induce anabolic functions in diseased articular cartilage. Methods We used reverse transcriptase–polymerase chain reaction, Western blot analysis, and immunohistochemistry to measure the expression of TFF3 in healthy articular cartilage, osteoarthritis (OA)–affected articular cartilage, and septic arthritis–affected articular cartilage and to assess the effects of cytokines, bacterial products, and bacterial supernatants on TFF3 production. The effects of TFF3 on matrix metalloproteinase (MMP) production were measured by enzyme-linked immunosorbent assay, and effects on chondrocyte apoptosis were studied by caspase assay and annexin V assay. Results Trefoil factors were not expressed in healthy human articular cartilage, but expression of TFF3 was highly up-regulated in the cartilage of patients with OA. These findings were confirmed in animal models of OA and septic arthritis, as well as in tumor necrosis factor α– and interleukin-1β–treated primary human articular chondrocytes, revealing induction of Tff3/TFF3 under inflammatory conditions. Application of the recombinant TFF3 protein to cultured chondrocytes resulted in increased production of cartilage-degrading MMPs and increased chondrocyte apoptosis. Conclusion In this study using articular cartilage as a model, we demonstrated that TFF3 supports catabolic functions in diseased articular cartilage. These findings widen our knowledge of the functional spectrum of TFF peptides and demonstrate that TFF3 is a multifunctional trefoil factor with the ability to link inflammation with tissue remodeling processes in articular cartilage. Moreover, our data suggest that TFF3 is a factor in the pathogenesis of OA and septic arthritis.

As ephrins have been associated with tumorigenesis and tumor progression, we investigated ephrin-A5 (EFNA5) expression in specimens of normal cartilage and chondrosarcomas of different grade by conventional and quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. We detected a significant EFNA5 down-regulation in chondrosarcomas compared with normal cartilage using quantitative RT-PCR (P < .05). The results were confirmed by Western blot and immunohistochemistry. We did not detect any causative genetic or epigenetic alterations in EFNA5 promoter methylation, loss of heterozygosity, or mutation analyses. Apart from slight differences in EFNA5 transcript amounts, we detected no significant influence of hypoxia on EFNA5 expression in C3842 and SW1353 chondrosarcoma cells. As EFNA5 down-regulation is a consistent finding in chondrosarcomas, we presume that it represents another essential alteration in tumorigenesis and tumor progression associated with cell adhesion, in addition to a multitude of other partially unknown biologic functions mediated by bidirectional ephrin/Eph receptor signaling and cross talk.

Odonto-onycho-dermal dysplasia (OODD), a rare autosomal-recessive inherited form of ectodermal dysplasia including severe oligodontia, nail dystrophy, palmoplantar hyperkeratosis, and hyperhidrosis, was recently shown to be caused by a homozygous nonsense WNT10A mutation in three consanguineous Lebanese families. Here, we report on 12 patients, from 11 unrelated families, with ectodermal dysplasia caused by five previously undescribed WNT10A mutations. In this study, we show that (1) WNT10A mutations cause not only OODD but also other forms of ectodermal dysplasia, reaching from apparently monosymptomatic severe oligodontia to Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors; (2) WNT10A mutations are a frequent cause of ectodermal dysplasia and were found in about 9% of an unselected patient cohort; (3) about half of the heterozygotes (53.8%) show a phenotype manifestation, including mainly tooth and nail anomalies, which was not reported before in OODD; and (4) heterozygotes show a sex-biased manifestation pattern, with a significantly higher proportion of tooth anomalies in males than in females, which may implicate gender-specific differences of WNT10A expression.