[Anatomy and physiology of the nasolacrimal ducts]. / Anatomie und Physiologie der ableitenden Tränenwege.

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.

[Avulsion of the Globe after Bicycle Accident--Clinical and Histopathological Evaluation]. / Avulsio bulbi nach Fahrradsturz - klinische und histopathologische Begutachtung.

BACKGROUND: Potential pathological mechanisms and complications of traumatic avulsio bulbi will be discussed based on the history, clinical, and histopathological findings of two patients. HISTORY AND SIGNS: Both patients were heavily affected by alcohol and had a bicycle accident with subsequent perforation of the upper eyelid by the handlebar-mounted hand brake levers. The accident resulted in disruption of the optic nerve and anterior displacement of the globe. THERAPY AND OUTCOME: In one patient, it was possible to reposition the globe into the orbit; however, the second patient's eye had to be enucleated. Functional testing demonstrated permanent loss of vision of the primary involved eyes, visual field defects, and visual impairment of one fellow eye. CONCLUSION: Avulsio bulbi describes a severe trauma to the eye often induced by sport and traffic accidents. Special attention should be addressed to the primary non-affected fellow eye with regard to potential functional defects.

Report of a new case with pentasomy X and novel clinical findings.

Pentasomy X is an extremely rare sex chromosome abnormality, a condition that only affects females, in which three more X chromosomes are added to the normally present two chromosomes in females. We investigated the novel clinical findings in a 1-year-old female baby with pentasomy X, and determined the parental origins of the X chromosomes. Our case had thenar atrophy, postnatal growth deficiency, developmental delay, mongoloid slant, microcephaly, ear anomalies, micrognathia and congenital heart disease. A conventional cytogenetic technique was applied for the diagnosis of the polysomy X, and quantitative fluorescent polymerase chain reaction (QF-PCR) using 11 inherited short tandem repeat (STR) alleles specific to the chromosome X for the determination of parental origin of X chromosomes. A cytogenetic evaluation revealed that the karyotype of the infant was 49,XXXXX. Comparison of the infant's features with previously reported cases indicated a clinically recognizable specific pattern of malformations referred to as the pentasomy X syndrome. However, to the best of our know-ledge, this is the first report of thenar atrophy in a patient with 49,XXXXX. The molecular analysis suggested that four X chromosomes of the infant originated from the mother as a result of the non disjunction events in meiosis I and meiosis II. We here state that the clinical manifestations seen in our case were consistent with those described previously in patients with pentasomy X. The degree of early hypotonia constitutes an important early prognostic feature in this syndrome. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non disjunctions.

[In vitro and in vivo investigations of a modified textile keratoprosthesis. ACTO TexKPRO]. / In-vitro- und In-vivo-Untersuchung einer modifizierten textilen Keratoprothese. ACTO TexKPRO.

BACKGROUND: Clinical application of a keratoprosthesis (KPRO) is still a challenging task. Recent developments reflect the concepts of nut and bolt, intrastromal implantation or an osteoodontokeratoprosthesis (OOKP). A new concept of a textile KPRO has been evaluated in a limited human study with considerable difficulties which after termination of the study and considerable improvements was restarted using animal experiments. MATERIALS: The ACTO TexKPRO is made from polyvinylidene difluoride (PVDF) fibers and transparent silicone. The first and second developmental stages differed in density and size of fibers and furthermore in surface modifications of the fibers and optics which were improved for the second prototype. METHODS: Implantation of the prosthesis was performed in four patients with corneal blindness and in two cases retinal disease which required surgery. In the later animal experiments surgery was performed on three rabbits. Surgery was performed by redressing the conjunctiva, opening of the eyeball with a central 6.5 mm trephination, removal of the lens and iris and implantation and suturing of the TexKPRO. If required a silicone oil endotamponade was placed. RESULTS: All eyes were stable with the keratoprosthesis. The first prototype showed conjunctival recession on the textile haptics with highly susceptible endopthalmitis risk due to infection of the PVDF so that we decided to remove the prosthesis from all eyes after one case of severe endophthalmitis occurred. The longest time of placement was 40 months and the shortest time 6 months. All eyes were restored by keratoplasty. In animals with the new haptic we found better conjunctivalization and stable implantation of the KPRO. DISCUSSION: The textile KPRO provides a stable implantation procedure and safe connection of fibers to the scleral wound bed. The optical and mechanical implantation is safe and stable. Surface epithelialization is improved with the new surface modifications and different PVDF fiber density but beforel new implantations are planned further conceptual changes will be introduced.

[Updated incidence of dry eye syndrome in Germany]. / Aktuelle Inzidenz des Trockenen Auges in Deutschland.

BACKGROUND: Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that compromise quality of life. The aim of the study was to find out when patients consult ophthalmologists in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS: 170 patients treated at ophthalmological practices in Bavaria, Saxony and Saxony-Anhalt with dry eye were surveyed regarding their symptoms. RESULTS: The majority of those questioned were 40 years of age or older (88 %) (average: 60), female (59 %) and described a variety of subjective symptoms (65 %). More than five different concurrent symptoms were named. There is a recognisable increase in cases - by more than 3.5 times - at the age of forty (in women) and fifty (in men). CONCLUSIONS: We hope to contribute with the data obtained to a more complete understanding of this highly complex pathological process. A further aim is to facilitate recognition of this mostly chronic condition in its early stages when the symptoms are still poorly defined. The data on the German population obtained here should become part of a comparative analysis within the international context. Despite considerable scientific effort, dry eye remains a difficult challenge for both patients and attending physicians.

[Trauma of periorbital soft tissue. Reconstruction with regard to functional and aesthetic aspects]. / Trauma der periorbitalen Weichteile. Rekonstruktion unter funktionellen und ästhetischen Gesichtspunkten.

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.

RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: These data suggest that RAGE is involved in the development of obesity and insulin resistance.

Rapid detection of fetal aneuploidies by quantitative fluorescent-polymerase chain reaction for prenatal diagnosis in the Turkish population.

Prenatal diagnosis is testing for diseases or conditions in a fetus or embryo before it is born. It employs a variety of techniques to determine the health and condition of an unborn fetus. The main goal of this process is to perform prenatal diagnosis at the earliest possible stage of gestation. In this regard, quantitative fluorescent-polymerase chain reaction (QF-PCR), a novel technique that is fast and reliable, was employed to detect aneuploidies (13, 18, 21, X and Y) without the need of the time-consuming culturing process. The QF-PCR method can detect five different chromosome aneuploidies with 98.6% accuracy. In this study, 1874 amniotic fluid samples of pregnant subjects, who were referred to the Department of Medical Biology and Genetics, Adana, Turkey (molecular biology section), were analyzed with the QF-PCR technique by employing 27 short tandem repeat (STR) markers to detect chromosomes 13, 18, 21, X and Y aneuploidies. We detected 31 subjects (1.7%) with aneuploidies or euploidies out of the 1874 subjects. The average age of the pregnant subjects was 32 (range: 14-49). Abnormal karyotypes detected were as follows: 47,XX,+21 (19.4%, 6/31), 47,XY,+21 (48.4%, 15/31), 48,XXX,+21 (3.2%, 1/31), 69,XXX (3.2%, 1/31), 47,XY,+13 (3.2%, 1/31), 47,XXY (9.6%, 3/31), 47,XXX (9.6%, 3/31) and 45,X (3.2%, 1/31). Moreover, some STR markers were found to be more specific to the Turkish population. In conclusion, QF-PCR can be regarded as an alternative method of conventional cytogenetic analysis as it is a rapid and reliable method; however, in most cases it is required to be supported or validated with conventional cytogenetic karyotyping and some STR markers employed for QF-PCR can be more informative for a given population.

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey.

Many clinical conditions, including osteoporosis, are associated with serum levels of sex steroids. Enzymes that regulate rate-limiting steps of steroidogenic pathways, such as CYP17 and CYP19, are also regarded as significant factors that may cause the development of these conditions. We investigated the association of two common polymorphisms, in the promoter region (T→C substitution) of CYP17 and exon 3 (G→A) of CYP19, with bone mineral density (BMD) in the lumbar spine and femoral neck and serum androgen/estradiol, in a case-control study of 172 postmenopausal women aged 62.3 ± 9.6 years (mean ± SD). The CYP17 TC genotype was significantly overrepresented in patients compared to controls, and TC genotype neck T-score and lumbar T-score values were significantly higher in patients compared to controls. CYP17 TC and TT genotype testosterone and DHEA-SO(4) levels were lower in patients compared to controls. All three genotypes of CYP19 had almost the same distribution among patients. The CYP19 AG genotype, however, was most frequent among controls. CYP19 lumbar BMD levels were close to each other among the different genotypes; however, AA and AG genotypes were significantly lower in patients. Testosterone and DHEA-SO(4) levels in the CYP19 GG genotype were higher compared to those of the other genotypes in patients but not in controls. CYP19 GA individuals had lower E(2) levels and lower BMD in controls and patients. Femoral neck BMD and lumbar T-score were also diminished with GA transition. In conclusion, CYP17 and CYP19 gene polymorphisms were found to be associated with osteoporosis in postmenopausal women in Turkey.

Retinal astrocytomas: long-term follow-up.

BACKGROUND: Retinal astrocytomas are exceedingly rare benign tumours of the retina. Their occurrence can be solitary or multiple, uni- or bilateral, isolated or in association with a phakomatosis such as tuberous sclerosis or neurofibromatosis type 1. PATIENTS AND METHODS: We report the long-term follow-up in three patients with retinal astrocytomas. RESULTS: Over many years of follow-up all astrocytomas showed very little progression and no deterioration of visual function. Subtle changes occurred inside the lesions. CONCLUSIONS: Even after long-term follow-up the natural course of retinal astrocytic hamartomas seems to be favourable, with visual loss and significant growth being unlikely to occur. A thorough ophthalmological and general evaluation, in order to rule out an underlying systemic disease and to document the ocular status, are needed initially. Thereafter eye examinations can be scheduled in long intervals.

Interlamellar cohesion after corneal crosslinking using riboflavin and ultraviolet A light.

AIMS: Collagen crosslinking treatment of progressive keratoconus using the photosensitiser riboflavin and ultraviolet A light of 370 nm wavelength has been shown to increase significantly the tensile strength of corneal collagen by about 300%. In keratoconus, interlamellar and interfibrillar slippage have been proposed as pathogenetic mechanisms. Therefore, the aim of this study was to assess the impact of collagen crosslinking on the interlamellar cohesive force. METHODS: 72 post mortem porcine eyes were divided into six different treatment groups: the untreated control group, the standard crosslinking group, the hypo-osmolar crosslinking group, the stromal swelling group, the formaldehyde group and the α-amylase group. An anterior 9×4 mm strip of 400 µm thickness was prepared using a lamellar rotating microkeratome. For interlamellar cohesive force measurements a splitting plane was created at 50% depth. Force-distance profiles were recorded using a microcomputer-controlled biomaterial testing machine. RESULTS: The mean interlamellar cohesive force was 0.24 N/mm in the untreated control group, 0.26 N/mm in the standard crosslinking group, 0.25 N/mm in the hypo-osmolar crosslinking group, 0.23 N/mm in hydrated corneas, 0.27 N/mm in the formaldehyde group without statistically significant difference. Only the values of the α-amylase group were statistically significantly lowered by 31.5% to 0.16 N/mm. CONCLUSIONS: Surprisingly, corneal crosslinking does not increase the interlamellar cohesive force. In the α-amylase group the cohesive force was mainly decreased because of the digestion of proteoglycans. Crosslinking seems to stabilise only inter- and intrafibrillar, but not interlamellar cohesion.

[Unilateral papilledema with contralateral loss of vision]. / Einseitiges Papillenödem und kontralateraler Visusverlust.

A 46-year-old woman presented with a 4-day history of headache, dizziness and blurred vision in the left eye and a 1-year history of neck pain. Fundoscopy revealed a pale optic disc in the left eye and a swollen optic disc in the right eye. Furthermore a bilateral anosmia was evident. Cranial magnetic resonance imaging (MRI) showed a mass in the anterior cranial fossa, which was classified as a WHO grade I endotheliomatous meningeoma. A Foster Kennedy syndrome was diagnosed.

Trefoil factor family peptide 3 at the ocular surface. A promising therapeutic candidate for patients with dry eye syndrome?

Dry eye syndrome is a widespread disease accompanied by discomfort and potential visual impairments. Basic causes are tear film instability, hyperosmolarity of the tear film, increased apoptosis as well as chronic inflammatory processes. During the last decades, our understanding of dry eye syndrome has considerably increased. However, the molecular mechanisms of the disease remain largely elusive. In this context, our group focuses on trefoil factor 3 (TFF3). Among other factors, TFF3 performs a broad variety of protective functions on surface epithelium. Its main function seems to be in enhancing wound healing by promoting a process called 'restitution'. Studies evaluating TFF3 properties and effects at the ocular surface using in vivo as well as in vitro models have revealed a pivotal role of TFF3 in corneal wound healing. Subsequent studies in osteoarthritic cartilage seem to draw a different picture of TFF3, which still needs further elucidation. This manuscript summarizes the findings concerning TFF3 in general and its role in the cornea as well as articular cartilage - two tissues which have some things in common. It also discusses the potential of TFF3 as a candidate therapeutic agent for the treatment of, for example, ocular surface disorders.

[Clinical course of a solitary retinal astrocytoma]. / Klinisch-zeitlicher Verlauf eines solitären retinalen Astrozytoms.

Retinal astrocytomas are benign tumors of the retina. Their localization can be solitary, multiple, or bilateral in both eyes. It is also known that they can be part of a phakomatosis syndrome (i.e., tuberous sclerosis or neurofibromatosis). Because retinal astrocytomas have a slow growth rate, yearly controls by an ophthalmologist with interdisciplinary consultation are adequate. Some uncommon cases have been reported in which the tumor has grown more aggressively. These tumors may require therapeutic interventions (e.g., vitreoretinal surgery, brachytherapy, photodynamic therapy, or cryotherapy).

[Unusual myopic fundus alteration]. / Ungewöhnliche myope Fundusveränderung.

A 44-year-old female patient reported a "black dot" which had been in front of the right eye for more than 4 days and which moved together with eye movements. The optical coherence tomography (OCT) image of the right macula showed large cystic cavities and thickening within the retinal pigment epithelium (RPE) near the fovea centralis as well as small bore cystic alterations, which indicated an event in the region of the choroid. Fluorescein angiography and indocyanine green angiography excluded choroidal neovascularization (CNV). The diagnosis revealed a broad superficial choroidal blood vessel mimicking a subretinal hemorrhage.

Loss of classical transient receptor potential 6 channel reduces allergic airway response.

BACKGROUND: Non-selective cation influx through canonical transient receptor potential channels (TRPCs) is thought to be an important event leading to airway inflammation. TRPC6 is highly expressed in the lung, but its role in allergic processes is still poorly understood. OBJECTIVE: The purpose of this study was to evaluate the role of TRPC6 in airway hyperresponsiveness (AHR) and allergic inflammation of the lung. METHODS: Methacholine-induced AHR was assessed by head-out body plethysmography of wild type (WT) and TRPC6(-/-) mice. Experimental airway inflammation was induced by intraperitoneal ovalbumin (OVA) sensitization, followed by OVA aerosol challenges. Allergic inflammation and mucus production were analysed 24 h after the last allergen challenge. RESULTS: Methacholine-induced AHR and agonist-induced contractility of tracheal rings were increased in TRPC6(-/-) mice compared with WT mice, most probably due to compensatory up-regulation of TRPC3 in airway smooth muscle cells. Most interestingly, when compared with WT mice, TRPC6(-/-) mice exhibited reduced allergic responses after allergen challenge as evidenced by a decrease in airway eosinophilia and blood IgE levels, as well as decreased levels of T-helper type 2 (Th2) cytokines (IL-5, IL-13) in the bronchoalveolar lavage. However, lung mucus production after allergen challenge was not altered by TRPC6 deficiency. CONCLUSIONS: TRPC6 deficiency inhibits specific allergic immune responses, pointing to an important immunological function of this cation channel in Th2 cells, eosinophils, mast cells and B cells.