Lutz Hesse

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas

Abstract · Purpose: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). · Methods: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 μg was performed. Gas instillation (0.2–0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). · Results: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 μg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). · Conclusion: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD.

Implantation of retina stimulation electrodes and recording of electrical stimulation responses in the visual cortex of the cat

Abstract Background: Simple basic visual perception may be restored by epiretinal electrical stimulation in patients that are blind due to photoreceptor loss. To stimulate ganglion cells, epiretinally flat platinum microelectrodes embedded in thin polyimide film were developed and tested in the cat. Methods: After remo-val of the lens and the vitreous body a thin microfilm electrode array was implanted through a corneoscleral incision in the cat eye (n=4). In two eyes no further attempt was made to fixate the tip of the electrode, which was pressed onto the retinal surface due to the tension of the curved polyimide film. In two eyes the tip of the electrode was fixed with cyanoacrylate adhesive. The exterior part of the microelectrode film was directed under the skin towards the forehead which allowed fixation of the microplug to a head fixation bolt. Retinal stimulation experiments were performed within 1 week after implantation. Success of stimulation was assessed by recording neuronal activities from areas 17 and 18. Retinal microelectrodes were removed 2 weeks or longer after implantation. Results: Intraocular inflammation or retinal detachment were not observed after implantation of the microelectrode film. In two eyes the tip of the microelectrodes dislocated spontaneously within the first few days. The lowest threshold of electrical stimulation was 35 µA, corresponding to a charge transfer of 14 nC per phase. These values were ten times higher than those obtained by needle electrodes used in prior experiments. Conclusions: Intraocular implanted flat microelectrodes made of platinum and polyimide were well tolerated. Because of the flat configuration of the microelectrodes higher stimulation thresholds than for needle electrodes were found, indicating insufficient con-tact to the retinal surface. An alter-native shape and fixation technique is required to minimise electrodes’ threshold of stimulation.

Visual resolution with retinal implants estimated from recordings in cat visual cortex.

We investigated cortical responses to electrical stimulation of the retina using epi- and sub-retinal electrodes of 20-100 microm diameter. Temporal and spatial resolutions were assessed by recordings from the visual cortex with arrays of microelectrodes and optical imaging. The estimated resolutions were approximately 40 ms and approximately 1 degrees of visual angle. This temporal resolution of 25 frames per second and spatial resolution of about 0.8 cm at about 1m and correspondingly 8 cm at 10 m distance seems sufficient for useful object recognition and visuo-motor behavior in many in- and out-door situations of daily life.

An Optically Powered Single-Channel Stimulation Implant as Test System for Chronic Biocompatibility and Biostability of Miniaturized Retinal Vision Prostheses

A microsystem based microimplant with an optically powered single-channel stimulator was designed and developed as test system for an epi-retinal vision implant. Biostability of the hybrid assembly and the encapsulation materials were evaluated in pilot experiments in chronic implantations in a cat animal model. The implant was fabricated on a flexible polyimide substrate with integrated platinum electrode, interconnection lines, and contact pads for hybrid integration of electronic components. The receiver part was realized with four photodiodes connected in series. A parylene C coating was deposited on the electronic components as insulation layer. Silicone rubber was used to encapsulate the electronics in the shape of an artificial intraocular lens to allow proper implantation in the eye. Pilot experiments showed the biostability of the encapsulation approach and full electric functionality of the microimplant to generate stimulation currents over the implantation period of three months in two cats. In one cat, electrical stimulation of the retina evoked neuronal responses in the visual cortex and indicated the feasibility of the system approach for chronic use

Silicone Oil for Recurrent Vitreous Hemorrhage in Previously Vitrectomized Diabetic Eyes

AIMS To investigate the clinical course of vitrectomized patients with recurrent diabetic vitreous hemorrhage who were treated by revitrectomy with silicone oil (SO) as a hemostyptic tamponade. PATIENTS AND METHODS Fifteen patients with recurrent vitreous hemorrhage due to proliferative diabetic vitreoretinopathy were included in this retrospective study. All eyes had had at least one vitrectomy prior to use of SO and the retina was completely attached at any time before revitrectomy with SO instillation. Thirteen patients had a blind fellow eye. There were 6 males and 9 females (mean age 62.7 years, range 45-76 years). The mean duration of SO tamponade was 25.8 months (range 9-35 months). The average follow-up period was 30.4 months (range 20-48 months). RESULTS Ten out of 15 eyes (66.6%) improved postoperatively, 9 eyes had a visual acuity of > or = 0.02 at the latest follow-up visit. Secondary glaucoma occurred in 4 eyes, leading to phthisis in 1 eye. All 5 phakic eyes developed a cataract. CONCLUSION A revitrectomy combined with a long-term hemostyptic SO tamponade offers a chance for restoration of useful visual acuity in diabetic eyes with persistent vitreous-hemorrhage that fails to subside after cryocoagulation and vitrectomy without tamponade. Because of possible visual loss from secondary glaucoma related to intraocular SO this treatment should mainly be considered in patients with a blind fellow eye.

Quantitative effect of intravitreally injected tissue plasminogen activator and gas on subretinal hemorrhage.

Purpose: To quantify the effect of intravitreally injected tissue plasminogen activator (TPA) and an expanding gas on freshly formed subretinal hemorrhage (SRH). Patients and Methods: Thirteen patients with acute (1 week or less) SRH due to age‐related macular degeneration (ARMD) were treated with an intravitreal injection of 50 &mgr;g TPA, and 24 hours later, with an expanding gas. Fundus photographs taken before and 24 hours after each injection were digitized and calibrated. Area, geometric center, and shift of the SRH were measured at each time point using NIH image analysis software. Elevation of the SRH was assessed by echography. Results: Compared to the preoperative size, SRH enlarged significantly 24 hours after TPA injection (P < 0.001). A significant shift of the geometric center toward the inferior retinal periphery out of the macula was found after gas injection (P < 0.001). Significant horizontal displacement of the SRH was not noted after TPA or gas injection. More elevated subretinal blood clots showed a larger increase in size after TPA injection than flat clots (P < 0.05). Conclusion: Enlargement of SRH in a gravity‐dependent manner indicates subretinal liquefaction of the clot after TPA treatment. An intravitreal injection of gas 24 hours later can significantly displace the SRH inferiorly. RETINA 20:500‐505, 2000

Populationsbezogene Erhebung zur diabetischen Retinopathie in Wolfsburg

ZusammenfassungHintergrund. Seit November 1997 wird im Rahmen eines Modellprojektes die vollständige Dokumentation einer ophthalmologischen Befundung bei Diabetikern durch die BKK-VW für Versicherte in Wolfsburg einmal jährlich vergütet. Methoden. Ergebnisse der Untersuchung wurden im Befundbogen der Initiativgruppe zur Früherkennung diabetischer Augenerkrankungen dokumentiert. Erfasst wurden Visus, Augeninnendruck, Linsenstatus sowie Fundusbefund. Ergebnisse. Es wurden ophthalmologische Befunde von 2.801 Patienten mit Diabetes mellitus erfasst. Eine Pseudophakie lag bei 357 Augen vor, 1.216 Augen hatten eine visusrelevante Katarakt oder einen Nachstar. Von 263 Patienten unter 40 Jahren hatten 18,8% eine milde oder mäßige und 3,3% eine schwere nicht proliferative diabetische Retinopathie (NPDR). In dieser Gruppe wurde eine proliferative diabetische Retinopathie (PDR) bei 2,2% gefunden. Von 2.228 Patienten älter als 40 Jahre hatten 11,9% eine milde oder mäßige und 2,6% eine schwere NPDR. Eine PDR wurde in dieser Gruppe bei 0,9% diagnostiziert. Schlussfolgerung. Die Implementierung einer jährlichen Vorsorgeuntersuchung auf der Basis des Befundbogens der Initiativgruppe war erfolgreich. Erstmals wurde Daten zur Prävalenz der diabetischen Retinopathie in einer populationsbezogenen Erhebung in einer deutschen Stadt gewonnen. Die Prävalenzraten liegen deutlich niedriger als in bisher publizierten vergleichbaren Studien benachbarter Länder.AbstractIntroduction. Since November 1997 the complete documentation of an ophthalmological examination of diabetics has been annually subsidised by the Volkswagen Corporation Health Maintenance Organization (VW-HMO). Methods. The results of an annual ophthalmological examination were recorded in a standardised history sheet developed by the Initiative Group for Early Detection of Diabetic Eye Diseases. These data included visual acuity, intraocular pressure, lens status and a description of fundus abnormalities. Results. Within 26 months ophthalmological examinations of 2,801 patients were completed which represented 4.5% of all VW-HMO insured patients. On average, patients suffered from diabetes for 9.6 years (SD±8.3), artificial intraocular lenses were present in 357 eyes (6.4%) and 1,216 eyes (12.0%) were diagnosed with cataract or posterior capsule opacification impairing visual acuity. Out of 263 patients younger than 40 years old, 18.8% had a mild or moderate and 3.3% a severe non-proliferative diabetic retinopathy (NPDR). A proliferative diabetic retinopathy (PDR) was found in 2.2% of the younger patients. Of 2,228 patients aged 40 years and older, 11.9% had a mild or moderate and 2.6% a severe NPDR. In 0.9% of this group PDR was diagnosed. Conclusions. An annual ophthalmological screening based on a survey sheet of the Initiative Group was successfully introduced. For the first time a population-based evaluation on the prevalence of diabetic retinopathy was carried out for inhabitants of a German city. The prevalence of PDR was found to be lower than previously published in comparable studies.

Muscarinic receptor functioning and distribution in the eye : molecular basis and implications for clinical diagnosis and therapy

Muscarinic receptor functioning and distribution in the eye: Molecular basis and implications for clinical diagnosis and therapy

Physiologische Funktionsprüfungen von Retinaimplantaten an Tiermodellen

ZusammenfassungRetinaimplantate sollen durch elektrische Stimulation der Retina bei blinden Patienten mit teilweise degenerierter Netzhaut (z. B. bei Retinitis pigmentosa) Seheindrücke erzeugen. Voraussetzung hierfür ist, dass die in der Retina elektrisch erzeugten Aktivitätsverteilungen auch korrekt in der Sehrinde abgebildet werden, so dass Form- und Bewegungssehen ermöglicht werden. In der Entwicklungsphase der Implantate werden die aufwendigen Erprobungs- und Optimierungsexperimente an Tiermodellen durchgeführt. Verwendete Tiermodelle im Retinaimplantat-Projekt des BMBF sind isolierte Netzhäute vom Hühnchen und der rezeptorgeschädigten Ratte sowie das narkotisierte Kaninchen, das Schwein und die Katze mit intakter Netzhaut. Die Untersuchungen zeigen, dass sowohl bei intakten als auch bei degenerierten Netzhäuten eine ortsaufgelöste Stimulation des neuronalen Netzwerkes möglich ist und geordnete Ganglienzellaktivität ausgelöst wird. Mit Registrierungen von Impulsaktivitäten mit penetrierenden Mikroelektroden direkt aus Area 17 der Sehrinde sowie durch Oberflächenableitungen von elektrisch evozierten Potenzialen der Sehrinde mit Makroelektroden konnte gezeigt werden, dass durch elektrische Stimulation in der Netzhaut tatsächlich die Sehrinde aktiviert wird.AbstractRetinal implants can – by electrical stimulation – create visual impressions in people with certain kinds of degenerative retinal diseases (e.g. Retinitis Pigmentosa). Electrically evoked potentials in the retina must be transferred into the visual cortex in an orderly manner, a prerequisite for any kind of form- and movement-perception. In the current developmental stage the difficult investigations are performed in various animal models: isolated retinae of intact chicken and of RCS-rats (a model for Retinitis Pigmentosa), as well as in anesthetised rabbits, pigs and cats with intact retinae. Our investigations show that spatially selective ganglion-cell responses can be recorded following focal electrical stimulation, in healthy and as well in degenerated retinae. Registration of activities in area 17 of the visual cortex demonstrate that electrical retinal stimulation can indeed activate it.

Einsatz von Enzymen im hinteren Augenabschnitt Derzeitiger Stand und zukünftige Möglichkeiten

ZusammenfassungDie enzymatische Behandlungsmethode von Erkrankungen im hinteren Augenabschnitt findet zunehmende Verbreitung. Derzeit wird durch intravitreal injizierten Gewebeplasminogenaktivator eine subretinale Blutung lysiert und mittels eines intravitreal injizierten Gases mechanisch aus der Makula verdrängt. Jüngste morphometrische Analysen konnten eindeutig eine subretinale Fibrinolyse nach intravitrealer Injektion von Gewebeplasminogenaktivator nachweisen. Damit konnte erstmals eine aufwendige Pars-plana-Vitrektomie durch ein enzymatisches Therapieverfahren ersetzt werden. Klinische Erfahrungen mit der Pars-plana-Vitrektomie zeigten, dass eine vollständige Entfernung des Glaskörpers einen günstigen Einfluss auf den Verlauf von vasoproliferativen vitreoretinalen Erkrankungen hat. Therapeutische Ziele einer enzymatischen Behandlung des Glaskörpers zielten daher entweder auf die Verflüssigung des Glaskörpers oder die Trennung der hinteren Glaskörperrinde von der Netzhaut. Insbesondere durch jüngste Erkenntnisse zur Pathophysiologie vasoproliferativer vitreoretinaler Erkrankungen ergeben sich neue therapeutische Optionen. Künftig wäre eine Behandlung des diabetischen Glaskörpers mit geeigneten Enzymen denkbar, um die Entstehung eines proliferativen Verlaufs der diabetischen Retinopathie zu verhindern.AbstractThe first investigations to treat diseases of the posterior segment enzymatically started 40 years ago. To treat acute subretinal hemorrhage a pneumatic displacement through intravitreally injected gas after enzymatically induced subretinal fibrinolysis (TPA) is recommended. Recent morphometric analysis clearly demonstrated a subretinal fibrinolytic effect after intravitreal injection of TPA. Obviously TPA crosses the retina through microlesions that develop through elevation of the retina during acute bleeding. For the first time pars plana vitrectomy was superseded by a simple and gentle enzymatic therapy combined with pneumatic displacement by intravitreally injected gas. Increasing experience with pars plana vitrectomy demonstrated that a complete removal of the vitreous body has beneficial effects on the course of vasoproliferative vitreoretinal diseases. Therefore enzymes were tested to either liquify the vitreous body (collagenase or hyaluronidase) or to cleave the posterior vitreous cortex and the retina (dispase, plasmin, tissue plasminogen-activator or chondroitinase). At present only tissue-plasminogen activator (TPA), plasmin and hyaluronidase were used in small clinical studies. Recent developments in the understanding of vasoproliferative vitreoretinal disorders offers new therapeutical approaches like enzymatical destruction of growth factors (VEGF) or extracellular adhesive proteins (fibronectin). From this point of view future therapies may include enzymatic cleaning of the vitreous body to prevent proliferative diabetic vitreoretinopathy.