[Polymorphisms of complement factor genes and age-related macular degeneration in a German population]. / Komplementfaktor-Polymorphismen und altersassoziierte Makuladegeneration in einer Gruppe deutscher Patienten.

BACKGROUND: An association of the Tyr402His variant of the complement factor H (CFH) gene with age-related macular degeneration (AMD) has been shown in several Caucasian populations, while studies for an association with other single nucleotide polymorphisms (SNP) of complement system genes have produced inconsistent results. We examined the distribution of several SNPs of complement system genes (CFH, C 2, C 3, factor B) in patients with exsudative AMD and healthy controls. PATIENTS/MATERIALS AND METHODS: 226 patients with exsudative AMD and 179 controls without AMD were included. Genomic DNA was extracted from saliva samples. RESULTS: A significant association with exsudative AMD was found only for SNP rs1061170 (Y402 H) in the CFH gene. For rs1047286 (P292L) and rs2230199 (R102G) in the C 3 gene, rs547154 (IVS10) and rs9332739 (E318D) in the C 2 gene and rs4151667 (L9 H) in CFB gene, no associations with exsudative AMD were found. CONCLUSIONS: We have replicated an association of the Y 402 H variant with exsudative AMD in our population. Although variants R 102G, IVS10, E 318D and L 9 H have been shown to be associated with AMD in earlier studies, we could not confirm these findings. The results show that AMD has variable association patterns with rare variants in different populations.

[Peripheral exudative haemorrhagic chorioretinopathy: clinical and angiographic findings]. / Periphere, exsudative hämorrhagische Chorioretinopathie: Klinische und angiografische Befunde.

BACKGROUND: Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is a degenerative disease of the peripheral retina and choroid in the elderly. Although PEHCR is often seen by clinicians, this entity is underrepresented in the ophthalmological literature. This may be due to inconsistent naming. PATIENTS: We present the clinical, ultrasonographic and angiographic findings of 11 eyes of 8 patients who were diagnosed with PECHR in our department between January 2006 and June 2008. In addition, we report the intra- and postoperative course of three eyes that have been vitrectomised because of a vitreous haemorrhage associated with PEHCR. RESULTS: The mean age of the patients is 83.5 years (range: 75 - 95). The mean follow-up is 11 months (range: 0 to 20). The clinical and angiographic signs were dependent on the stage of the disease and may be seen as small asymptomatic peripheral subretinal bleeding and exudation. In advanced stages, vitreous haemorrhage and exudative retinal detachment may be observed. The temporal periphery of the fundus appears to be more often affected than other locations. Three patients were affected bilaterally. Vitreous haemorrhage was the reason for presentation in three eyes (27 %) that were treated successfully by vitrectomy. CONCLUSIONS: Peripheral exudative hemorrhagic chorioretinopathy should be considered in the differential diagnosis of vitreous haemorrhage and peripheral subretinal tumors in the elderly.

[Visual acuity after cataract surgery in patients with age-related macular degeneration]. / Visusverlauf nach Kataraktoperation bei Patienten mit altersassoziierter Makulopathie.

BACKGROUND: To analyze changes in visual acuity after cataract surgery in patients suffering from age-related maculopathy. MATERIAL AND METHODS: This retrospective case-control study included all patients who had consecutively undergone phacoemulsification from January 2000 to February 2006, had a preexisting diagnosis of early age-related macular degeneration (AMD), and were followed up for at least 1 year postoperatively (n=1,152 eyes of 696 patients). The control group comprised phakic patients diagnosed with early AMD from January 2000 to February 2006 who did not undergo eye surgery and were followed up for at least 1 year (n=334 eyes of 202 patients). RESULTS: In 62.1% of operated eyes, the best-corrected visual acuity was at least two logMAR units better than before surgery, and in 26.7% it was at least four logMAR units better. Deterioration of visual acuity of more than four logMAR units occurred in 1.3% of operated eyes and 1.5% of control eyes. CONCLUSION: Cataract surgery can markedly improve visual acuity in patients with age-related maculopathy.

[Pseudoangiitis in bilateral ocular ischemia]. / Pseudoangiitis bei beidseitiger okulärer Ischämie.

BACKGROUND: The term 'frosted branch angiitis' was initially used to describe an idiopathic form of vasculitis in association with panuveitis. It has since also been used to describe the angiographic phenomenon of diffuse leakage along retinal vessels against the background of other ocular and systemic diseases. METHODS: We describe a 57-year-old male patient with acute bilateral reduction of visual acuity, headaches and absence of any pulse at the temporal arteries. Fluorescence angiography showed bilateral diffuse leakage along all the retinal vessels, which resembled frosted branches. Laboratory parameters and histology were not indicative of vasculitis. Imaging showed complete occlusion of both common carotid arteries and a hypoplastic vertebral artery on the left. CONCLUSIONS: Ocular ischemia may imitate primarily inflammatory conditions in its angiographic appearance.

Band keratopathy: a modified treatment.

PURPOSE: The surgical treatment of band keratopathy usually consists of abrasion of the corneal epithelium followed by removal of the subepithelial calcium deposits by means of an ethylenediamine-tetraacetic acid (EDTA) solution. In order to reduce the discomfort and pain that occur after corneal abrasion, the authors developed a modified technique that avoids the abrasion of the epithelium. METHODS: In three patients (four eyes) with long-standing band keratopathy, the epithelium was detached with a 19% ethanol solution and placed gently toward the limbus, a method also used in laser-assisted subepithelial keratectomy (LASEK). After clearing the anterior stroma with EDTA solution, the epithelial flap is unrolled and a bandage contact lens applied. RESULTS: Postoperative pain was greatly reduced and after removal of the contact lens no pain was reported. CONCLUSIONS: This modified epithelium-sparing treatment of band keratopathy shows good results while reducing postoperative pain.

[Uveitis and the aging]. / Die Uveitis des alternden Menschen.

Uveitis can be found in all age groups, but the age of disease onset may provide important information on the etiology of the disease. New data on the epidemiology of uveitis disclose a higher incidence and prevalence in older patients then has previously been found. Masquerade syndromes which mimic uveitis may be found especially in younger and older patients. These have to be excluded from regular intraocular inflammation. Here, intraocular lymphoma plays a major role which is most often associated with severe clinical, diagnostic and therapeutic challenges. One of the major complications of uveitis is cataract formation. Keeping in mind the importance of pre- and postoperative treatment, even implantation of an intraocular lens in older patients with uveitis is currently a safe procedure.

Fluorescence videomicroscopic assessment of xenogeneic microcirculation and impact of antibody removal by immunoadsorption.

BACKGROUND: Alterations in microcirculation are considered central to the pathogenesis of hyperacute xenogeneic rejection (HXR) of vascularized xenografts, but currently there exist no data describing these microhemodynamic alterations. METHODS: Rat livers were perfused in situ with either isogeneic rat blood or xenogeneic human blood. The microcirculation of these xenoperfused livers was investigated directly using intravital fluorescence microscopy, and compared with that of isogeneic hemoperfused livers. In addition, the impact of antibody depletion by immunoadsorption was investigated. RESULTS: Although a homogenous microcirculation was found during isogeneic liver perfusion (index of acinar perfusion 90.4%/sinusoidal perfusion rate 93.6%), xenoperfusion resulted in a rapid breakdown of the microcirculation (47.5%/67.1%, respectively). Perfusion deficits were found predominantly in the periportal areas. Immunoadsorption reduced the total amount of IgM and IgG by 75.2% and 96.2%, respectively, and caused a significantly improved liver perfusion (80.2%/84.4%) and liver function, as indicated by bile production. In contrast, the massive hepatic leukocyte and platelet accumulation observed during perfusion with untreated xenogeneic blood was not altered by antibody depletion. CONCLUSIONS: Thus, the combination of isolated rat liver perfusion and intravital fluorescence microscopy enables the observation and quantification of the early phase of HXR. This is an important step forward for sensitive characterization of the rejection process and will enable the mechanisms involved in HXR to be elucidated. Antibody depletion was shown to improve liver function and perfusion, but did not reconstitute liver viability to the level of the isogeneic perfusion. These findings highlight the need for additional therapeutic regimens in xenografting.

In vivo study of leukocyte-endothelium interaction in endotoxin-induced uveitis.

PURPOSE: To analyze leukocyte-endothelium interaction in iris venules of living rats and to quantify changes of leukocyte dynamics in endotoxin-induced uveitis (EIU). METHODS: Lewis rats received an intraperitoneal injection of 100 micrograms of lipopolysaccharide (LPS; Salmonella typhimurium). Using intravital fluorescence microscopy, the iris vessels were examined, 2, 4, 6, 10, 14, 24, and 72 hours after LPS injection. A setup for intravital fluorescence microscopy of iris venules in the rat is described. Images are recorded with a video camera and stored on S-VHS videotape for off-line analysis. For contrast enhancement, erythrocytes and plasma were stained with fluorescein isothiocyanate (FITC) and FITC-hydroxyethylstarch, respectively. Rhodamine 6G was used for intravital staining of leukocytes. Resolution and magnification (x850) of the system facilitates observation of individual cells in the bloodstream in real time. Leukocytes were either flowing in the center stream, rolling along the endothelium, or firmly adherent. Image analysis provided data on microvascular leukocyte flux and leukocyte velocity. RESULTS: The percentage of leukocytes rolling on postcapillary venular endothelium increased significantly (P < 0.05) 4 hours after endotoxin administration, as did the number of firmly adherent cells. Leukocyte-endothelium interaction reached its maximum 6 to 10 hours before an increase of inflammatory cells in the aqueous humor. The response to endotoxin was reversible, subsiding to near-normal values after 72 hours. CONCLUSIONS: Intravital fluorescence microscopy provides data on microvascular parameters, including the number of rolling and sticking leukocytes on vascular endothelium. Inflammation of the anterior uvea was characterized with regard to leukocyte recruitment from blood to the vessel wall.

Delayed mustard gas keratopathy: clinical findings and confocal microscopy.

PURPOSE: To describe the clinical manifestations and confocal microscopic findings in a patient with delayed mustard gas keratopathy. METHOD: Case report. A 32-year-old veteran who had participated in the Iran Iraq conflict was exposed to mustard gas in 1988. Ocular abnormalities in 1996 and 1998 and corneal confocal microscopic findings in 1998 are presented. RESULTS: In 1996, slit-lamp examination disclosed bilateral limbal changes with tortuous blood vessels and full-thickness corneal alterations. In 1998, the right eye had porcelain-white episcleral changes and adjacent peripheral ulcerative keratopathy. Confocal microscopy demonstrated irregular-appearing epithelial and basal epithelial cells. The anterior stroma was remarkable for spindle-like keratocytes, diffuse fibrillar inhomogeneities and the presence of highly reflective material. CONCLUSIONS: Mustard gas keratopathy is a uncommon cause of ocular damage, but it may lead to delayed ocular damage.

Tumour necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulcerations.

BACKGROUND/AIMS: Ultrastructural alterations in the stroma adjacent to corneal perforations have previously been reported in patients with longstanding rheumatoid arthritis. Since patients with rheumatoid arthritis often present upregulation of proinflammatory cytokines in serum and in synovial fluid, it was of interest to analyse the gene expression of these cytokines-for example, tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), in corneal samples from patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis. METHODS: Corneal samples from seven patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis were collected in 4% paraformaldehyde in "RNAse-free" conditions. Paraffin sections were fixed on silan coated slides and further analysed by systematic non-radioactive in situ hybridisation, using specific gene probes for TNF-alpha and IL-6 labelled with digoxigenin (DIG). Detection of hybrids was carried out by using a commercially available DIG detection system. RESULTS: Whereas an extended TNF-alpha gene expression could be clearly observed in the keratocytes surrounding the corneal ulcerations and/or perforations from five of the seven analysed patients, all seven patients presented clearly positive results for an extended IL-6 gene expression in the analysed tissue samples. CONCLUSIONS: Alterations in corneal cells surrounding ulcerations and/or perforations in patients with rheumatoid arthritis may occur with implication for inflammatory processes. Upregulation of the proinflammatory cytokines TNF-alpha and IL-6 may modify the production of metalloproteinases in the corresponding cells resulting in collagenolytic corneal damage.

Detection of tumor necrosis factor alpha and interleukin 1 alpha gene expression in human lens epithelial cells.

PURPOSE: To analyze the gene expression of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) in human lens epithelial cells (LECs) by in situ RNA hybridization. SETTING: Department of Ophthalmology and Laboratory for Molecular Biology, Charité, Humboldt University, Berlin, Germany. METHODS: Anterior lens capsules with attached LECs were collected in RNase-free conditions from 10 consecutive patients during cataract surgery. Samples were then systematically analyzed by an in situ RNA-hybridization technique using specific gene probes for IL-1 alpha and TNF alpha, which were previously labeled with digoxigenin (DIG). RESULTS: The LECs tested positive for DIG-labeled gene probes in the described conditions. One (10%) patient showed a clearly detectable IL-1 alpha gene expression, and 7 (70%) showed a widely positive reaction for TNF alpha mRNA. CONCLUSION: The TNF alpha gene expression in LECs was more extended than that of IL-1 alpha in lens capsule samples from cataract surgery. Active synthesis of TNF alpha and IL-1 alpha may have consequences for postoperative inflammation and LEC proliferation.

[Macrophage depletion inhibits leukocyte recruitment in experimental melanin-induced uveitis (EMIU)]. / Makrophagendepletion hemmt die Leukozytenrekrutierung bei experimenteller Melanininduzierter Uveitis (EMIU).

BACKGROUND: To study the role of macrophages in experimental melanin-induced uveitis (EMIU), we used the method of intravital microscopy to analyse changes in leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with liposomal clodronate. MATERIALS AND METHODS: EMIU was induced in Lewis rats (n = 48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated with liposomal clodronate (DMDP-lip) or empty liposomes on days -2, +1, 4, 6 and 8. Using IVM, postcapillary iris venules of rats were examined to quantify leukocyte rolling and firm adhesion to the vascular endothelium. RESULTS: Depletion of macrophages caused a decreased percentage of rolling leukocytes on day 8 (2 +/- 1.1% vs 15.2 +/- 1.6%, DMDP-lip vs EMIU, mean +/- SEM, ANOVA, p < 0.05) and day 10 (2.6 +/- 0.3% vs 14.2 +/- 1.6%). A significant decline in the number of firmly adherent leukocytes was detected on days 8 and 10 (88 +/- 13/mm2 vs 175 +/- 18/mm2 and 129 +/- 13/mm2 vs 372 +/- 31/mm2, DMDP-lip vs EMIU). Treatment with empty liposomes showed no changes in leukocyte firm adhesion. CONCLUSIONS: Elimination of macrophages prevents the induction of EMIU. In autoimmune-mediated uveitis, macrophages play a crucial role in the initiation of leukocyte-endothelium interaction.

[Apparent wall shear rate and leukocyte-endothelium interaction in iris blood vessels in endotoxin-induced uveitis]. / Scheinbare Wandscherrate und Leukozyten-Endothel-Interaktion in Irisgefässen bei Endotoxin-induzierter Uveitis.

UNLABELLED: Inflammatory stimuli induce the expression of adhesion molecules on leukocytes and endothelial cells. The adhesive forces between leukocytes and the vascular endothelium are antagonized by the shear stress of the flowing blood. The aim of this study was to examine how differences in the apparent wall shear rate measured in iris venules with varying caliber affect leukocyte-endothelium interaction. METHODS: The microvasculature of the iris in Lewis rats (n = 6) was examined using intravital fluorescence microscopy [2]. Blood flow was visualized with FITC-HES and leukocytes were stained with rhodamine 6G. Venules (n = 110) ranging in diameter from 20-60 microns were analysed with regard to the following parameters: Flux of leukocytes, velocity of leukocytes in the center stream, number of rolling and adherent leukocytes. The apparent wall shear rate was calculated from the center stream velocity and the vessel diameter. Animals were examined 4 h after administration of endotoxin from S. typhimurium (500 mg/kg body wt i.p.), when leukocyte-endothelium interaction is strongly enhanced. RESULTS: The flux of leukocytes, the absolute number of rolling leukocytes and the velocity of leukocytes in the center stream was higher in larger than in smaller venules. The apparent wall shear rate decreased with increasing vessel diameter. Calculated values were 806 +/- 59 s-1 for vessels 20-30 microns in diameter and 483 +/- 34 s-1 for vessels of 50-60 microns (mean +/- SEM). The number of adherent leukocytes per mm2 endothelial surface and the rolling fraction did not show significant differences between vessels with varying caliber. CONCLUSION: Although the shear rate declined with increasing vessel diameter, we could not observe an increase in rolling and adherent leukocytes. The effects of vessel diameter on leukocyte adhesion to the vascular endothelium in postcapillary iris venules are minimal.

[In vitro bovine and human lens epithelial cell culture studies on inhibition of posterior capsule opacification using a cyclic RGD peptide]. / In-vitro-Untersuchungen an bovinen und humanen Linsenepithelzellkulturen zur Nachstarhemmung mittels eines zyklischen RGD-Peptids.

BACKGROUND: RGD peptides competitively inihibit adhesion molecules of the lens epithelial cells (LEC). The purpose of our study was to investigate whether this peptide is capable of detaching adherent cells and preventing posterior capsule opacification (PCO). METHODS: Cultures of bovine and human LECs on culture dishes and discs of bovine anterior lens capsules were used. The inhibition of adhesion and the detachment of confluent LEC layers by the cyclic RGD peptide cRGDdFV were studied (incubation time was 3 days and 1 h and concentrations of 10(-4) and 10(-3) M were used). RESULTS: A dose-dependent inhibition of adhesion (48% and 42%, respectively) was obtained. There was a significant difference between the control peptide group and cRGDdFV (p < 0.0001). Cell detachment from lens capsules was not achieved but complete detachment from the culture dish occurred after 37 min. CONCLUSIONS: Short-term incubation of LECs by cRGDdFV did not lead to a sufficient inhibition of adhesion in vitro. A detachment of adherent LECs by cRGDdFV was not achieved.

[Practical significance of critical fusion frequency (CFF). Chronological resolution of the visual system in differential diagnosis]. / Praktische Bedeutung der Flimmerfusionsfrequenz (CFF). Zeitliche Auflösung des visuellen Systems in der Differenzialdiagnose.

The value of measuring the critical fusion frequency (CFF) as part of ophthalmological diagnostics is examined. The relevant literature on changes of the CFF concomitant with refraction errors, media opacity, age-related macular degeneration, glaucoma and various other opticopathies is discussed regarding the relevance of CFF for the differential diagnosis. Various methods and instruments for measuring the CFF are presented. The CFF is a complex function of the visual system and changes in CFF cannot be ascribed to a specific level of signal transduction. However, measurement of the CFF is a valuable test in the clinical routine to estimate potential visual acuity in the presence of media opacity and to screen for lesions of the optic nerve. Reduction of CFF in an eye that otherwise appears normal may prompt the ophthalmologist to initiate further examination facilitating diagnosis of specific conditions, such as optic neuritis, before visual acuity is reduced. Measuring the CFF is technically simple, inexpensive and fast and can be delegated to medical personnel. Measurement of the CFF should be an integral component of routine ophthalmological examinations.

[Headache and diplopia in an extremely obese adolescent]. / Kopfschmerzen und Doppelbilder bei einem Jugendlichen mit extremer Adipositas.

BACKGROUND: The prevalence of idiopathic intracranial hypertension is increased in overweight children and adolescents. CASE REPORT: In a fifteen-year old, extremely obese adolescent with a history of headache and diplopia treatment with acetazolamide resulted in relief of the neurological symptoms.

[Posterior segment complications of laser in situ keratomileusis (LASIK)--a survey of the literature]. / Hinterabschnittskomplikationen der Laser-in-situ-Keratomileusis (LASIK)--Eine Literaturübersicht.

During the past years refractive surgical procedures and particularly laser IN SITU keratomileusis (LASIK) have become established by clinical and experimental studies and are performed worldwide in a high number. This paper provides a survey of the published posterior segment complications of LASIK that may occur albeit very rarely. Additionally, current clinical and experimental hypotheses regarding the pathogenesis of those complications are discussed. Currently a cause-effect relationship between LASIK and reported posterior segment complications has not been proven although a very high number of LASIK procedures have been performed worldwide.