Burkhard Dick

Retinal vascular occlusion and deficiencies in the protein C pathway

PURPOSEnTo report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion.nnnMETHODSnIn a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also screened 209 consecutive inpatients with deep vein thrombosis from the same geographic region for resistance to activated protein C as well as protein C and protein S deficiencies.nnnRESULTSnTen (29%) of 35 patients with central retinal vein occlusion (CRVO) had factor V R506Q mutation. The factor V R506Q mutation was detected in four (19%) of 21 patients with branch retinal vein occlusion. The higher frequency in factor V R506Q mutation compared with the expected 9% mutation prevalence in a white population was highly significant for the central retinal vein occlusion group but not for the branch retinal vein occlusion group. In all patients with resistance to activated protein C, the factor V R506Q mutation was detected; 16 were heterozygous, one homozygous. No cases of lupus anticoagulants, protein C, or protein S deficiencies were detected. Forty (19%) of 209 patients with deep vein thrombosis were carriers of the factor V R506Q mutation.nnnCONCLUSIONSnThe prevalence of the factor V R506Q mutation is similar in patients with central retinal vein occlusion and patients with deep vein thrombosis and represents a relevant risk factor. Screening for this mutation is therefore recommended in all patients with central retinal vein occlusion.

Accuracy and accommodation capability of a handheld autorefractor

PURPOSEnTo determine the accuracy of measurement by the Nikon Retinomax handheld autorefractor and its ability to relax accommodation.nnnSETTINGnPediatric Section, Department of Ophthalmology, University of Mainz, Germany.nnnMETHODSnTo perform a series of comparative measurements, autorefractor readings were obtained on healthy young adults (students) and on children aged 2 to 12 years. The autorefractor readings were compared with subjective refractions of the young adults and with cycloplegic retinoscopy of the children.nnnRESULTSnIn adults, the accuracy of the handheld autorefractor measurements was comparable to that of conventional tabletop autorefractors. In children, the autorefractor measurements performed under cycloplegia were reliable; when cycloplegic agents were not administered, 24% were overcorrected by more than -2.0 diopters.nnnCONCLUSIONnCycloplegia is often necessary to obtain accurate autorefractor results.

Analysis of the Antibody Repertoire in Tears of Dry-Eye Patients

Purpose: It has recently been suggested that dry-eye disease has an underlying autoimmune mechanism. This hypothesis is further supported by the successful treatment of the disease with immunomodulatory drugs such as cyclosporin A. Although it is known that tears contain antibodies, very little is known about the antibody repertoires in tears. It was the aim of this study to analyze the IgA antibody repertoire against ocular antigens in the tears of patients suffering from dry-eye disease and compare it to those of healthy volunteers. Methods: Two groups were examined: 20 healthy volunteers (controls) and 28 patients suffering from dry-eye disease. The patients were grouped according to the results of the basic secretory test. Patients with values ≤10 and subjective symptoms were classified as dry-eye patients. All tears were tested against Western blots of ocular antigens. For each Western blot, a densitograph was built by digital image analysis, and subsequently a multivariate discriminate analysis was performed. Results: A complex staining pattern was found in the tears of both dry-eye patients and healthy controls. However, the number of peaks was statistically significantly increased (p < 0.05) in the tears of dry-eye patients. The discriminant analysis found a statistically significant difference between the antibody repertoires of both groups (Wilks’ λ = 0.11; p < 0.001). Conclusions: In this study, it could be shown that the complex antibody repertoires in the tears of patients suffering from dry-eye disease are different from those found in the tears of healthy volunteers. Thus, our findings support the hypothesis that the dry eye disease has an autoimmune mechanism.

Inflammatory response after phacoemulsification treated with 0.5% prednisolone acetate or vehicle

PurposeTo compare the inflammatory response after phacoemulsification and intraocular lens implantation, using postoperative treatment with 0.5% prednisolone acetate eye drops or vehicle.DesignA multi-center randomized double-masked vehicle-controlled, parallel group phase IV study.MethodsSixty-two eyes of 62 patients undergoing phacoemulsification were examined at five German university eye hospitals (Mainz, Heidelberg, Bonn, Erlangen, Frankfurt/Main). Patients received either 0.5% prednisolone acetate eye drops (group 1) or vehicle eye drop solution (group 2) four times a day until day 2, then open-label treatment with 0.5% prednisolone acetate eye drops four times a day continued until day 14 for all patients. Postoperative inflammation was evaluated by using laser flare photometry. Secondary efficacy variables included visual acuity, intraocular pressure, corneal edema, bulbar conjunctival hyperemia and ocular discomfort.ResultsIn group 1, median flare rose from 7.4 photon counts/ms preoperatively to 31.0 photon counts/ms at day 1. In group 2, the flare increased from 8.6 photon counts/ms preoperatively to 30.5 photon counts/ms at day 1. The differences between the groups were not statistically significant. At day 3, flare measures were reduced in group 1 but remained fairly unchanged in group 2 (20.8 photon counts/ms vs 32.6 photon counts/ms), which was statistically significant (pu2009=u20090.0055). At day 14, photon counts were comparable in both groups (13.0 photon counts/ms vs 11.4 photon counts/ms), respectively. Both groups were comparable regarding secondary efficacy variables.Conclusions0.5% prednisolone acetate appeared to be significantly more effective as vehicle in controlling intraocular inflammation after phacoemulsification; both groups had a similar safety profile.

A new method for direct detection of heparin on surface-modified intraocular lenses : A modification of Jaques' toluidine blue staining method

BACKGROUNDnExamination of surface-bound heparin on synthetic polymers can only be performed by few staining methods. These methods are limited by an only approximate detection of heparin visible at high magnification. Other methods only measure heparin quantitatively (per square dimension) and are rather sensitive to artifacts. Due to its homogeneous staining pattern, the modified toluidine blue staining technique, using a non-protein-based substance, allows examination and analysis of the homogeneity of the monomolecular heparin layer even under critical conditions like scanning electron microscopy.nnnMATERIALS AND METHODSnFor critical examination of the heparin layer, this method was used for 5 sterile heparin surface-modified (HSM) monofocal (Pharmacia, 809C, 5 mm optical zone), 2 multifocal PMMA (Pharmacia, 811E, 6 mm optical zone) and 1 standard PMMA intraocular lenses (IOLs; Pharmacia, 809P, 5 mm optical zone). A special mixture containing a sodium borate buffer was used to avoid cross-reactions of toluidine with phenylimines, which permit a covalent surface linkage of heparin to synthetic polymeric materials via reductive amination. This resulted in less coarse-grained complex agglutination. After light and spectral microscopy of the surface of stained IOLs, scanning electron microscopy was performed to investigated the reliability and validity of this modified staining method.nnnRESULTSnAll HSM IOLs showed a homogeneous heparin structure and coating, which could be demonstrated even under critical photographic circumstances.nnnCONCLUSIONSnThe modification of the original toluidine blue staining method introduced by Jaques in 1943 is a reliable and reproducible technique for the detailed in vitro analysis of surface-bound heparin with a low artifact rate. Because of the detailed detection of heparin on polymeric surfaces, this staining method is recommended for special problems, e.g. in cataract surgery.

Einsatz von Mitomycin C bei Trabekulektomien mit reduzierter Prognose

ZusammenfassungDer Antimetabolit Mitomycin C wird bei Trabekulektomien mit erhöhtem Vernarbungsrisiko intraoperativ appliziert. Als Risikofaktoren für eine Sickerkissenvernarbung dürfen ein Patientenalter unter 40 Jahren, vorangegangene Entzündungen, eine durch Voroperationen oder durch langjährige antiglaukomatöse Therapie beeinträchtigte Bindehaut und eine starke Pigmentierung angesehen werden.Es wurde der postoperative Verlauf von 54 konsekutiv mittels Trabekulektomie mit Mitomycin C (MMC) operierten Augen von 50 Patienten mit erhöhtem Vernarbungsrisiko über durchschnittlich 49,6 Wochen (24 bis 185 Wochen) erfasst und ausgewertet. Das durchschnittliche Alter der Patienten betrug 52,1 Jahre (2 bis 93 Jahre). Vor der Trabekulektomie waren im Mittel 1,6 Operationen und 0,8 Argonlaser-Trabekuloplastiken vorgenommen worden. Präoperativ wurden im Mittel 2,9 Antiglaukomatosa (Wirkstoffgruppen) verwendet. Der präoperative Augeninnendruck (IOD) betrug 29,3 ± 8,2 mmHg mit Therapie und 36,0 ± 10,0 mmHg ohne Therapie. Bei jedem Auge wurde eine Trabekulektomie mit limbusbasalem Bindehautlappen und 5-minütiger Applikation von 0,1 ml MMC der Konzentration 0,2 mg/ml vorgenommen. Die Nachkontrollen erfolgten nach 1, 3, 6, 12 und 24 Wochen sowie 12 und 18 Monate postoperativ.Der mittlere IOD nach 24 Wochen betrug 14,3 ± 5,6 mmHg. Bei 39% der Augen kam es zu passageren Hypotonien mit Ausbildung einer serösen Aderhautschwellung, in einem Fall zu einer chorioidalen Hämorrhagie. Längere Hypotoniephasen von mehr als 6 Monate wurden bei zwei Augen beobachtet. Hornhautkomplikationen waren selten und bildeten sich in allen Fällen nach entsprechender Therapie zurück. Bei 34 Augen waren postoperativ weitere Eingriffe wie z. B. Fadendurchtrennung, Needling, Revisions-Trabekulektomie oder Sickerkissenübernähung erforderlich. 16 Augen bedurften einer medikamentösen IOD-Senkung. Nur bei 10 Augen (19%) war der IOD innerhalb der ersten sechs Monate postoperativ ohne weitere operative oder medikamentöse Maßnahmen reguliert.SchlussfolgerungDie Trabekulektomie mit intraoperativer Gabe von MMC führte in unserem Kollektiv von Augen mit hohen Vernarbungsrisiko zu einer guten Senkung des Augeninnendrucks. Allerdings erwiesen sich regelmäßige postoperative Kontrollen als erforderlich, um den Behandlungserfolg zu sichern. Lokale toxische Komplikationen durch Mitomycin C traten selten auf.SummaryThe antifibrotic agent mitomycin C is used as an adjunct in trabeculectomies with poor surgical prognosis. Risk factors for scrarring of the filtering bleb are age under 40 years, previous inflammations, distinct pigmentation and conjunctival scarring due to previous operations or prolonged antiglaucomatous therapy.54 eyes of 50 patients were examined for a mean follow-up period of 49.6 weeks (24 to 185 weeks). Mean age of the patients was 52.1 years (range 2–93 years). Trabeculectomy was preceded by 1.6 operations and 0.8 argon laser trabeculoplasties. The patients had a mean intake of 2.9 antiglaucomatous drugs. Before surgery, the intraocular pressure with and without medication was 29.3 ± 8.2 mmHg and 36.0 ± 10.0 mmHg, respectively. Trabeculectomies were performed using a limbus-based conjunctival flap. A volume of 0.1 ml mitomycin C (concentration: 0.2 mg/ml) was applied for 5 minutes prior to entering the eye. Postoperatively, the course was examined after 1, 3, 6, 12, 24 weeks and 12 as well as 18 months.Mean intraocular pressure after 24 weeks was 14.3 ± 5.6 mmHg. In 39% of the eyes a transient hypotony with choroidal detachment occurred, in one eye a hemorrhagic choroidal detachment was observed. Prolonged hypotonies of more than 6 months were seen in two eyes. Corneal epithelial defects were rare.In 34 eyes further surgical treatment was required, including suture lysis, needling, revision of trabeculectomy, surgical revision after leakage or cataract extraction. In 16 eyes, antiglaumatous drugs had to be applied. In only 10 eyes (19%) no further treatment, neither medical nor surgical, was necessary.In our group of glaucoma patients with poor surgical prognosis trabeculectomy with intraoperative application of mitomycin C induced a good lowering of the IOP. Nevertheless, regular postoperative controls were necessary. Complications due to localized tissue toxicity were rare.

Diskussion unter Berücksichtigung der eigenen Ergebnisse

Die Rasterelektronenmikroskopie ist bestens geeignet als Methode zur Beurteilung von Oberflachenstrukturen. In der Ophthalmochirurgie wurde sie erstmals von Drews et al. (1978), spater von Dersch (1981) eingesetzt, um Inhomogenitaten in der Oberflachenbeschaffenheit von Intraokularlinsen nachzuweisen, ferner wurde mikrochirurgisches Operationsinstrumentarium im Rahmen der Qualitatskontrolle rasterelektronenmikroskopisch untersucht (Adams, 1991; Thornton, 1991; Eisenmann und Jacobi 1993b).

Spezielle operative Aspekte der Kleinschnitt-Kataraktchirurgie bei Implantation multifokaler IOL

Der hohe Standard und die Sicherheit bei der Entfernung der Linse und Implantation der Intraokularlinse mit weitestgehender Perfektionierung der Techniken ruckt die Bedeutung im Umgang mit dem vorbestehenden Astigmatismus in den Vordergrund des Interesses. Im Rahmen der praoperativen Vorbereitung ist also auch die Erfassung des Astigmatismus und die danach ausgerichtete Wahl der entsprechenden Operationstechnik zur Erlangung des gewunschten postoperativen Astigmatismus wichtig. Hierbei lassen sich grob schematisch in Abhangigkeit vom praoperativen Astigmatismus, verschiedene Ziele unterscheiden: korneale Spharizitat zu erhalten, masigen Astigmatismus geringfugig und hohen Astigmatismus deutlich zu senken. Diese Ziele lassen sich entweder durch die Wahl einer bestimmten Inzision oder durch zusatzliche Masnahmen, wie z.B. astigmatische Keratotomien, erreichen.

Viskoelastika: Medizinprodukt oder Arzneimittel?

In § 2 Abs. 3 Ziff. 7 Arzneimittelgesetz (AMG) ist geregelt, das solche Stoffe, die dem Medizinproduktegesetz (MPG, 1994) unterfallen, nicht Arzneimittel im Sinne des AMG sind. Als Medizinprodukte werden in § 3 Abs. 1 MPG Stoffe definiert, deren bestimmungsgemase Hauptwirkung weder auf pharmakologischem oder immunologischem Gebiet liegt noch durch Metabolismus erzielt wird.

Substanzen für Viskoelastika

Hyaluronat (Abb. 26) kommt in nahezu allen Bindegeweben von Vertebraten vor und besteht aus einem verhaltnismasig langen linearen Polysaccharidmolekul (Balsasz et al., 1970). Es wird in der Zellmembran ohne Proteinbeteiligung synthetisiert und die lange lineare Polysaccharidkette wird direkt in die extrazellulare Matrix extrudiert (Prehm, 1984). Natriumhyaluronat dient der Zell- und Gewebsstabilisierung und spielt eine wichtige Rolle wahrend der embryonalen Entwicklung und des Wachstums. Auf Zellebene spielt Natriumhyaluronat bei der interzellularen Interaktion, Zellmatrixadhasion, Zellmobilitat und der extrazellularen Organisation eine gewisse Rolle. Weiterhin wird die Wundheilung beschleunigt (Abatangelo, Martelli & Vecchia, 1983; Arzeno & Miller, 1982). Es stellt die naturliche biologische Benetzungssubstanz dar.