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ZusammenfassungIn diesem Artikel sollen die Grundlagen zur Verwendung intraokularer Tamponaden in der Glaskörper-/Netzhautchirurgie bei Ablatio retinae und anderen Pathologien anhand zusätzlichen Videomaterials anschaulich dargestellt werden. Behandelt werden die verschiedenen Gase, Silikonöle und flüssigen Perfluorocarbone mit ihren Indikationen, ihrer Anwendung und insbesondere der intraoperativen Handhabung mit Fallstricken und Komplikationen. Charakteristische Animationen zeigen dabei nachvollziehbar die Prinzipien in der chirurgischen Handhabung. Seitens der beiden Erstautoren ist dieser Artikel ihrem Lehrer Herrn Prof. Dr. V.-P. Gabel gewidmet, der in den frühen 90er-Jahren die ersten Vitrektomiekurse für Augenärzte an der Universitäts-Augenklinik Regensburg erfolgreich im jährlichen Rhythmus etabliert hat und in denen viele heute noch netzhautchirurgisch tätige Kolleginnen und Kollegen ihre ersten Schritte in diesem Segment erlernt haben. Die weiteren Co-Autoren partizipierten unter seiner Leitung an jährlichen Vitrektomie-Wetlabs im Rahmen der Augenärztlichen Akademie Deutschlands.

This article is intended to clearly present the basic principles for the use of intraocular tamponades in vitreous/retinal surgery in the event of retinal detachment and other pathologies using additional video footage. It examines the various gases, silicone oils and perfluorocarbon liquids with their indications, administration and in particular intraoperative handling including pitfalls and complications. Characteristic animations show the principles of use in surgery in a comprehensible way. The two lead authors dedicate this article to their teacher Prof. Dr. V.-P. Gabel, who in the early 1990s successfully established the first vitrectomy courses for ophthalmologists at Regensburg University Eye Clinic each year. Many colleagues who still work in retinal surgery today first started learning about this segment on these courses. The other coauthors participated under his supervision in annual vitrectomy wet labs run by the German Academy of Ophthalmology.In diesem Artikel sollen die Grundlagen zur Verwendung intraokularer Tamponaden in der Glaskörper-/Netzhautchirurgie bei Ablatio retinae und anderen Pathologien anhand zusätzlichen Videomaterials anschaulich dargestellt werden. Behandelt werden die verschiedenen Gase, Silikonöle und flüssigen Perfluorocarbone mit ihren Indikationen, ihrer Anwendung und insbesondere der intraoperativen Handhabung mit Fallstricken und Komplikationen. Charakteristische Animationen zeigen dabei nachvollziehbar die Prinzipien in der chirurgischen Handhabung. Seitens der beiden Erstautoren ist dieser Artikel ihrem Lehrer Herrn Prof. Dr. V.-P. Gabel gewidmet, der in den frühen 90er-Jahren die ersten Vitrektomiekurse für Augenärzte an der Universitäts-Augenklinik Regensburg erfolgreich im jährlichen Rhythmus etabliert hat und in denen viele heute noch netzhautchirurgisch tätige Kolleginnen und Kollegen ihre ersten Schritte in diesem Segment erlernt haben. Die weiteren Co-Autoren partizipierten unter seiner Leitung an jährlichen Vitrektomie-Wetlabs im Rahmen der Augenärztlichen Akademie Deutschlands.

Purpose To investigate the influence of treatment regularity with intravitreal aflibercept injections (IVT-AFL injections) on visual acuity (VA) outcomes in patients with neovascular age-related macular degeneration (nAMD) enrolled in the PERSEUS trial who received at least 7 IVT-AFL injections during the first year. Methods This was a post hoc analysis of the PERSEUS trial, a prospective, non-interventional, multicenter cohort study, and included 370 patients with nAMD who had received ≥ 7 IVT-AFL injections during year 1. In addition to the prespecified subgroups of treatment-naïve and previously treated patients, results were compared between patients with regular (n = 209) and irregular (n = 161) treatment. Regular treatment was defined as initial dosing with monthly IVT-AFL injections for 3 months, then bimonthly IVT-AFL injections until month 12. Irregular treatment was defined as any deviation from regular treatment (provided ≥ 7 injections were received). The outcome of primary interest was the mean change in VA from baseline after 12 months. Further outcomes of interest included VA gain or loss, proportion of patients achieving reading vision, and percentage of patients with fluid. Results At month 12, the mean (± standard deviation, SD) VA improvement from baseline was 6.1 ± 15.6 Early Treatment Diabetic Retinopathy Study letters in the regular cohort and 2.5 ± 16.7 letters in the irregular cohort with ≥ 7 IVT-AFL injections (P = 0.0514). Best results were obtained in the treatment-naïve regular sub-cohort with a mean ± SD VA improvement of 8.0 ± 17.7 letters, whereas treatment-naïve patients with irregular treatment experienced a considerably lower VA gain (2.8 ± 20.0 letters). Irregular treatment consistently correlated with inferior results in treatment-naïve patients. At month 12, the proportion of treatment-naïve patients who had experienced a worsening of ≥ 5 letters was 29.6% in the irregular sub-cohort versus 13.6% in the regular sub-cohort (P = 0.0049). However, among the treatment-naïve patients, the mean number of injections was significantly higher in the irregular than in the regular sub-cohort (8.0 ± 1.2 vs. 7.4 ± 0.6; P = 0.0001). Furthermore, compared with the treatment-naïve, regular sub-cohort, patients in the irregular sub-cohort had more visits (19.1 ± 8.6 vs. 16.1 ± 5.7), VA tests (14.2 ± 6.9 vs. 12.0 ± 4.6), and optical coherence tomography examinations (5.1 ± 3.7 vs. 3.4.0 ± 3.0). Conclusions Although irregularly treated patients received more injections and more monitoring visits during the first year of IVT-AFL treatment, they experienced worse VA outcomes than regularly treated patients.

Purpose To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main Outcome Measures The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was –175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.

Purpose To evaluate the real-world effectiveness of intravitreal aflibercept injections in Germany in patients with neovascular age-related macular degeneration over 24 months. Methods PERSEUS was a prospective, non-interventional cohort study. The primary endpoint was the mean change in visual acuity (VA) from baseline. Secondary endpoints included the proportion of patients with a VA gain or loss of ≥ 15 letters and the frequency of injections and examinations. Patients with regular (bimonthly after 3 monthly injections during year 1 and ≥ 4 injections in year 2) and irregular (any other) treatment were analyzed. The last observation carried forward (LOCF) and the observed cases (OC) approach was applied for primary endpoint analysis to account for missing data. Results 803 patients were considered for effectivity analysis. At month 24, only 38% of the patients were still under observation. The LOCF population included 727, the OC population 279 patients. Treatment-naïve patients improved by 6.3 (LOCF)/8.1 (OC) letters with regular treatment over 24 months but only by 3.3 (LOCF)/3.1 (OC) letters with irregular treatment. The proportion of treatment-naïve patients achieving a VA improvement of ≥ 15 letters was similar between regularly and irregularly treated cohorts. However, considerably more patients in the irregular cohorts experienced a VA worsening of ≥ 15 letters than in the regular cohorts (LOCF: 18.7% vs. 7.4%). Conclusions Regular IVT-AFL treatment resulted in better VA outcomes than irregular treatment at month 24. However, only a minority of patients received regular treatment over a 2-year period.

Purpose To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. Design A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. Participants Patients (n = 848) with nAMD treated with IAI. Methods Patients (n = 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naive and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. Main Outcome Measures The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. Results Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naive patients and −0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naive patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes—an average VA gain of 8.0±17.7 letters—were seen in treatment-naive patients in the regularly treated population, whereas irregularly treated, treatment-naive patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs. −1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P = 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. Conclusions After 12 months of treatment with IAI, treatment-naive patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.

Zusammenfassung Hintergrund Prospektive kontrollierte Studien zur Behandlung des diabetischen Makulaödems (DME) mit Anti-VEGF-Therapeutika zeigen ein sehr gutes Visusergebnis über mehrere Jahre hinweg. Bisher liegen kaum Daten über Ergebnisse in der klinischen Behandlungsrealität vor, obwohl aus anderen Indikationsbereichen bekannt ist, dass die Ergebnisse der klinischen Routine oft denen aus prospektiven, kontrollierten Studien in Visusergebnis und Anzahl an Injektionen hinterherhinken. Wir berichten über eine Fallserie der Behandlung des DME an unserer Klinik. Patienten/Material und Methoden Retrospektive Fallserie von 335 Fällen mit einer Nachbeobachtungszeit von bis zu 3 Jahren. Fälle aus einem Zentrum, die wegen eines visusrelevanten diabetischen Makulaödems mindestens 1 Lucentisinjektion erhalten haben, wurden unter Auswertung des Verlaufs der zentralen Sehschärfe sowie der Anzahl von Injektionen ausgewertet. Ergebnisse Es findet sich ein mittlerer Gewinn an Sehschärfe im 1. und 2. Jahr von + 5,6 bzw. + 3,7 Buchstaben im Vergleich zur Baseline bei einem Ausgangsvisus von logMAR 0,52 (dezimal 0,3). Der Visusgewinn wird hauptsächlich in den ersten 4 Monaten erreicht, danach findet sich noch bis Monat 16 ein weiterer, jedoch flacherer Anstieg der Sehschärfe. Die mittlere Anzahl von Injektionen lag im 1., 2. und 3. Jahr bei 5,7, 3,2 und 1,1 Injektionen. Schlussfolgerung Die Daten zeigen einen Unterschied in der Behandlungsrealität des DME im Vergleich zu prospektiven, kontrollierten Studien, wie er bereits bei anderen Indikationen der Anti-VEGF-Therapie gefunden wurde: Der initiale Visusgewinn fällt geringer aus als in kontrollierten Studien und er kann nicht vollständig über längere Zeit gehalten werden. Diese geht einher mit einer deutlich geringeren Anzahl an Injektionen als in kontrollierten Studien. Gründe können in unterschiedlichen Patientenpopulationen liegen sowie in einer Negativselektion im Langzeitverlauf. Barrieren, die darüber hinaus eine zügige und bedarfsgerechte Therapie behindern, müssen weiter identifiziert und möglichst umgangen werden.

Zusammenfassung Hintergrund Die statistische Beurteilung klinischer Fallserien ist nicht ohne Schwierigkeiten. Scheinkorrelationen können bei der Analyse entstehen, wenn der Zusammenhang zwischen nur einer einzelnen Einflussgröße und der Zielgröße untersucht wird. Häufig ist dies der Fall, wenn sogenannte konfundierende Variablen (d. h. weitere Variablen, welche das Ergebnis beeinflussen) nicht berücksichtigt werden. In prospektiven Studien werden diese Variablen entweder so weit als möglich kontrolliert, oder sie werden durch Randomisierung zwischen den Gruppen ausgeglichen. In retrospektiven Auswertungen kann diese Technik nicht angewendet werden. Stattdessen sollte eine multivariate Analyse durchgeführt werden, die alle bekannten und dokumentierten Variablen berücksichtigt. Patienten/Material und Methoden Statistische Evaluation der Einflussgrößen auf das Visusergebnis am Ende des 2. Jahres einer Anti-VEGF-Therapie an einem Datensatz aus 1300 nvAMD-Fällen (nvAMD: neovaskuläre altersabhängige Makuladegeneration). Die folgenden Einflussgrößen (Variablen) wurden untersucht: Ausgangsvisus, Netzhautdicke zur Baseline, Alter bei Baseline, mittleres Visitenintervall, Anzahl an Injektionen, Visusgewinn nach dem Upload sowie ein Wechsel des Anti-VEGF-Präparats. Zielgröße war der Gewinn oder Verlust der Sehschärfe als Letter Score am Ende des 2. Jahres. Ergebnisse Alle untersuchten Variablen haben einen deutlichen Einfluss auf das Visusergebnis, sofern nur einzelne Regressionen untersucht werden. Eine initiale Analyse des Einflusses einer Therapieumstellung zeigt einen scheinbar großen Einfluss auf den Visusverlauf. Die multivariate Analyse zur Vermeidung von Scheinkorrelationen zeigt jedoch, dass nur die folgenden Variablen das Visusergebnis statistisch signifikant beeinflusst haben: Ausgangsvisus, Visusgewinn nach dem Upload, Anzahl an Injektionen, Visitenintervall sowie Netzhautdicke zur Baseline. Die Therapieumstellung selbst hat keinen statistisch signifikanten Einfluss auf das Visusergebnis. Schlussfolgerungen Die Umstellung der Anti-VEGF-Therapie ist nicht ursächlich für einen besseren Visusverlauf. Bei der statistischen Analyse von nicht randomisierten, retrospektiven Daten ist es besonders wichtig, konfundierende Variablen zu berücksichtigen. Sind die untersuchten Subgruppen nicht für diese Variablen ausgeglichen, können Scheinkorrelationen entstehen, die nicht die tatsächlichen Zusammenhänge abbilden.

Zusammenfassung Hintergrund Die Behandlungswirklichkeit der neovaskulären altersbedingten Makuladegeneration (nvAMD) unterscheidet sich hinsichtlich Injektionsintervallen und langfristiger Visusstabilität von kontrollierten prospektiven Studien. Real-Life-Daten zeigen, dass in der klinischen Routine engmaschige Kontroll- und Wiederbehandlungsintervalle oft nicht eingehalten werden. Wir analysieren an einer Fallserie die tatsächlichen Intervalle für Kontrollen und Wiederbehandlung und untersuchen, wie sich verlängerte Intervalle unmittelbar auf den Visusverlauf auswirken und welche Konsequenzen dies für den langfristigen Visuserhalt hat. Patienten/Material und Methoden Retrospektive Fallserie von 1324 Augen mit nvAMD, die über einen Beobachtungszeitraum von bis zu 3 Jahren 8150 Ranibizumab-Injektionen (nach PRN-Schema) bzw. 1725 Aflibercept-Injektionen (nach festem Schema) erhalten haben. Die Intervalle zwischen aufeinanderfolgenden Visiten, der Visusverlauf und die Anzahl der Injektionen im Therapieverlauf wurden ausgewertet. Ergebnisse Die angestrebten Intervalle zwischen einzelnen Visiten von 4 bzw. 8 Wochen werden im PRN-Schema häufiger überschritten als im fixen Schema. Im Durchschnitt ist der maximale Visusanstieg nach einer Injektion nicht nach 4 Wochen, sondern erst nach etwa 6 – 8 Wochen erreicht. Ein statistisch signifikanter Unterschied zwischen Aflibercept und Ranibizumab wurde nicht gefunden. Die besten Visusergebnisse nach 1 und 2 Jahren werden mit einem durchschnittlichen Wiederbehandlungsintervall von 4 – 6 Wochen erreicht. Verlängerte Intervalle gehen mit schlechterem Langzeitvisus einher. Das fixe Schema zeigt auch im Therapieverlauf im 2. und 3. Jahr kürzere Re-Injektionsintervalle und bessere Visusergebnisse als das PRN-Schema. Schlussfolgerungen Unsere Daten zeigen, dass engmaschige Nachkontrollen und kurze Behandlungsintervalle wichtig und wesentliche Einflussfaktoren für die Visusergebnisse sind. Insgesamt erscheint die Wahl eines Therapieschemas, das dies ermöglicht, wichtiger als die Wahl des Präparates selbst.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess changes in retinal structure and thickness after subretinal implantation of the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany). PATIENTS AND METHODS: Spectral-domain optical coherence tomography (SD-OCT) imaging was performed to assess the structure and thickness of the retina anterior to the microphotodiode array preoperatively, within 6 weeks and 6 months ± 1 month after implantation. Thickness measurements were performed using the distance tool of the built-in software. Three thickness measurements were performed in each of the four quadrants of the retina on the microchip within 6 weeks and 6 months ± 1 month after implantation. RESULTS: The mean ± standard deviation change in retinal thickness from within 6 weeks to 6 months ± 1 month after implantation in all four quadrants combined was 24 μm ± 68 μm. None of the tested variables (location, time, or their interaction) had a statistically significant effect on the mean retinal thickness ( P = .961, P = .131, and P = .182, respectively; n = 19). CONCLUSION: The authors report on qualitative and quantitative findings in retinal structure in 27 patients after subretinal implantation of the Retina Implant Alpha IMS using OCT technology. No significant changes of retinal thickness could be observed in a period of 6 months after surgery. With more patients receiving subretinal implants and with advanced OCT technology, the data set will be extended to study possible changes in retinal structure in finer detail. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:993–999.]

ZusammenfassungDie Therapie der neovaskulären altersabhängigen Makuladegeneration (nvAMD) mit Inhibitoren des vaskulären endothelialen Wachstumsfaktors hat sich seit Einführung in Deutschland deutlich verbessert. In verschiedenen Anwendungsbeobachtungen zum Einsatz von Ranibizumab und Aflibercept in Deutschland hat sich in den letzten Jahren – parallel zur steigenden Behandlungsfrequenz – ein verbesserter Funktionsgewinn am Ende des 1. Behandlungsjahrs gezeigt. Dies spiegelt sich z. T. auch in retrospektiven Fallserien wider. Mit längeren Verlaufszeiträumen, z. B. für eine Nachbeobachtung von mehr als 3 Jahren, stellt sich trotz des initialen Visusgewinns ein zunehmender Funktionsverlust ein, sodass langfristig nur der Ausgangsvisus gehalten werden konnte. Eine Therapieverzögerung ist vor allem im ländlichen Bereich und bei einer Betreuung an verschiedenen Einrichtungen (z. B. mehreren Praxen oder Praxis und Klinik) ein Problem. Erfreulicherweise weisen hier aktuellere Auswertungen auf eine positive Entwicklung hin. Therapieverzögerung wurde reduziert, Therapie- bzw. Injektionsfrequenz erhöht und Therapieergebnisse verbessert. Dieser Trend muss sich fortsetzen, damit optimale, unter Routinebedingungen zu erreichende Therapieergebnisse in Deutschland erzielt werden.

Purpose To evaluate the motility of the eye in patients with the RETINA IMPLANT Alpha AMS. Methods Eye motility was determined in eight gaze directions in ten blind retinitis pigmentosa patients, who had received the RETINA IMPLANT Alpha AMS, before implantation of the subretinal implant and at six time-points up to one year after. Results The analysis of eye motility showed a restriction in the upgaze and gaze to the temporal side directly after surgery in eight of the nine patients included. The degree of motility restriction decreased continuously with recovery during the observation time. One year after surgery, eye motility was still restricted in the majority of patients, especially in the upgaze to the temporal side at 20° (five of seven patients). Conclusion Retinal implants with intraorbital parts (e.g. connecting cables) caused restriction in the temporal and superior viewing directions in the majority of patients. Although this restriction might be cosmetically visible, this limitation in eye motility has no effects on the monocular vision and the implant's efficacy for daily use.

Purpose Electronic retinal implants restore some visual perception in patients blind from retinitis pigmentosa. Eye movements cause mechanical stress in intraorbital power supply cables leading to cable breaks. By using computer tomography (CT) scans at the extreme positions of the four cardinal gaze directions, this study determined in vivo, which of three surgical routing techniques results in minimal bending radius variation and favors durability. Methods Nine patients received the first-generation subretinal implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) in one eye. Three techniques for intraorbital cable routing were used (straight cable route (A), parabulbar loop (B), and encircling band (C)), each in three patients. All patients underwent computer tomography of the orbital region. The bending radius of the intraorbital cable was measured with the DICOM viewer Osirix v4.1.2 (Pixmeo SARL, Bernex, Switzerland) and served as indicator for mechanical stress. Results Average bending radius variation was 87% for method A, 11% for method B, and 16% for method C. Methods A and B (P = 0.005) and methods A and C (P = 0.007) differed significantly, while method B and C showed no statistical difference (P = 0.07). Conclusions Compared to straight routes, arcuated cable routes significantly reduce cable movement and bending. Due to an easier surgical procedure, a parabulbar loop is the preferred method to minimize bending radius variation and prolong survival time of electronic subretinal implants. Translational Relevance CT analysis of cable bending of implanted medical devices allows to determine which surgical routing technique favors durability in vivo.

Purpose of review The purpose of this review is to provide an update on the efforts to restore vision through subretinal implants in patients with degenerative retinal diseases. In addition to the current technique and its latest improvements, it will focus on the surgical technique of implantation as well as explantation and reimplantation. Recent findings The durability of the current subretinal implant RETINA IMPLANT Alpha AMS has increased substantially compared with the predecessor model RETINA IMPLANT Alpha IMS. According to validated examinations in the laboratory, a median lifetime of 4.7 years will be reached in clinical use; in similar examinations, the previous model has reached only 8 months. Visual function has slightly increased. The surgical technique for subretinal implants is complex and demanding for ophthalmic surgeons, as it is multifaceted and combines novel surgical steps in areas, which are not commonly entered such as the suprachoroidal and the subretinal space. The surgical approach for implantation has matured considerably and has led to successful implantation in 64 patient cases. Surgical challenges are now mainly encountered with the exact subfoveal positioning of the device. The explantation procedure is relatively straight-forward because the implant can be withdrawn in a reverse direction along the already existent subretinal path. Reimplantations, however, are more challenging because some degree of scar tissue may exist along the path of the chip and around the scleral trapdoor. Nevertheless, reimplantations have now been carried out successfully in four patients. Summary The new RETINA IMPLANT Alpha AMS shows significantly improved durability compared with the predecessor model RETINA IMPLANT Alpha IMS. The subretinal implant offers excellent visual results but requires experienced surgeons. Explantation of devices is straight-forward, and reimplantations are challenging but have been successful in four patients.

A subretinal visual implant (Alpha IMS, Retina Implant AG, Reutlingen, Germany) was implanted in 29 blind participants with outer retinal degeneration in an international multicenter clinical trial. Primary efficacy endpoints of the study protocol were a significant improvement of activities of daily living and mobility to be assessed by activities of daily living tasks, recognition tasks, mobility, or a combination thereof. Secondary efficacy endpoints were a significant improvement of visual acuity/light perception and/or object recognition (clinicaltrials.gov, NCT01024803).During up to 12months observation time twenty-one participants (72%) reached the primary endpoints, of which thirteen participants (45%) reported restoration of visual function which they use in daily life. Additionally, detection, localization, and identification of objects were significantly better with the implant power switched on in the first 3months.Twenty-five participants (86%) reached the secondary endpoints. Measurable grating acuity was up to 3.3 cycles per degree, visual acuities using standardized Landolt C-rings were 20/2000, 20/2000, 20/606 and 20/546. Maximal correct motion perception ranged from 3 to 35 degrees per second. These results show that subretinal implants can restore very-low-vision or low vision in blind (light perception or less) patients with end-stage hereditary retinal degenerations.

To restore vision in patients with retinitis pigmentosa, several types of electronic devices have been developed to stimulate neurons at different levels along the visual pathway. Subretinal stimulation of the retina with the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) has been demonstrated to provide useful vision in daily life. Here we evaluated the safety of this device.An interventional, prospective, multi-center, single-arm study was conducted in patients with retinitis pigmentosa with the Retina Implant Alpha IMS. The results from the first nine patients of a single center regarding safety of the device are reported. Any untoward medical occurrence related or unrelated to the tested device was documented and evaluated.Nine adult subjects were included in the study at the Tübingen site. Seventy-five adverse events occurred in total, and 53 affected the eye and its adnexa. Thirty-one ocular adverse events had a relationship to the implant that was classified as "certain" while 19 had a probable or possible relationship; three had no relationship to the implant. Thirty-nine ocular adverse events resolved without sequelae, two resolved with sequelae, 11 remained unresolved, and in one the status was unknown. The intensity of ocular adverse events was mild in the majority of cases (n = 45), while six were of moderate and two of severe intensity. There was no non-ocular adverse event with certain relationship to the device. One subject lost light perception (without light localization) in her study eye.In conclusion, this prospective study, "Safety and Efficacy of Subretinal Implants for Partial Restoration of Vision in Blind Patients," shows that the Retina Implant Alpha IMS is an option for restoring vision using a subretinal stimulation device with a clinically acceptable safety profile.

The subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tubingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.

A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes (‘chip’), each with its own amplifier and local stimulation electrode. At the implant's tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron–electrode interface. Visual scenes are projected naturally through the eye's lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.

BACKGROUND: Heavier than water tamponades offer the possibility to support the inferior part of the fundus after retinal detachment. The aim of this study was to evaluate the anatomic and functional outcome of complicated retinal detachment treated with vitreous surgery and heavy silicone oil (HSO) tamponade. Surgery was performed in eyes with rhegmatogenous retinal detachment (RD) predominantly in the lower hemisphere or with penetrating injury (either as primary intervention or after development of proliferative vitreoretinopathy [PVR]). MATERIALS AND METHODS: Sixty-one eyes of 61 patients with RD - mostly complicated by PVR - and a minimum follow-up of 12 months were included in this study. Vitreoretinal surgery with HSO (Oxane HD) tamponade was performed in all patients. In 52 patients, heavy silicone oil was used in the management of complicated RD. 9 patients had surgery for complicated RD after penetrating eye injury.The mean follow-up period was 30.3 +/- 10.2 months. RESULTS: The overall final anatomic success rate was 79 %. In 39 % of the cases the retina remained attached during the entire follow-up period. CONCLUSIONS: The anatomic success rate after surgery with HSO (Oxane HD) was relatively low; however, only complex cases bearing a higher risk of retinal re-detachment received HSO in this study. Oxane HD does not appear to have major advantages compared to conventional silicone oil or other new-generation heavy silicone oils in these cases.

To describe functional and morphological long-term follow-up results in patients with idiopathic macular telangiectasia (IMT) treated with intravitreal bevacizumab. Retrospective case series of three consecutive male patients with IMT who were treated with intravitreal bevacizumab injections. Best corrected visual acuity (BCVA) as well as fluorescein angiography (FA) and optical coherence tomography (OCT) were monitored over the period of up to 12 months. Single intravitreal bevacizumab injection resulted in a marked increase in BCVA from 20/50 to 20/20 in the patient with type 1 (aneurysmal) IMT during the first 4 weeks. Late-phase leakage on FA and cystoid macular oedema on OCT decreased significantly. This was sustained over the whole follow-up period of 12 months. In contrast, in the two patients with type 2 (perifoveal) IMT, leakage on FA decreased likewise, but this was not accompanied by an increase in BCVA despite triple injections. Small cystic changes seen on OCT remained unchanged. Patients with type 1 IMT with pronounced macular oedema on OCT may benefit from intravitreal bevacizumab injections, showing functional as well as morphological improvement, while patients with type 2 IMT with minimal cystic changes on OCT do not show functional improvement despite repeated injections.

The purpose of this study was to characterise an ex-vivo adult porcine retina-retinal pigment epithelium (RPE) perfusion organ culture model. Fresh porcine full-thickness retina-RPE-choroid tissue samples were clamped into tissue carriers and mounted in two-compartment containers. The retinal and choroidal sides were continuously perfused with culture medium. pO(2), [Na(+)], [K(+)], [Cl(-)], [glucose], [lactate], and pH were measured in the medium. Tissue samples were examined after 24h, 4, 7, and 10 days in culture. The morphology of the retina and the RPE was examined by light and electron microscopy (LM, EM). The retinal cellular integrity was further examined by immunohistochemistry (Ki 67, GFAP, rhodopsin, synaptophysin, syntaxin, NF 200, TUNEL-test). Fresh porcine full-thickness retina-RPE-choroid tissue samples and tissue samples in static organ culture served as controls. LM, EM, and immunohistochemistry showed intact retinal and RPE cytoarchitecture kept in perfusion culture. Photoreceptor outer segments showed first signs of degeneration after 24h, significant signs of apoptosis and necrosis appeared in the retina after 4 days in perfusion culture. Control tissue samples kept in static culture showed disintegration of the retinal cytoarchitecture after 4 days in culture. The data show that adult porcine retina-RPE tissue can be maintained morphologically intact in perfusion organ culture for at least 10 days. Although first signs of degeneration set in after 24h the structural preservation of the tissue in perfusion organ culture is superior to that in static culture. The perfusion culture model of the retina refines organotypic in vitro test systems and may help to reduce the number of necessary animal experiments in retina and RPE research. It offers new perspectives for the safety testing of substances designed for intraocular application.

Seit 2004 wird die Krankenhausbehandlung offener Augenverletzungen in der DRG C01Z als Fallpauschale abgerechnet. Da das Ausmas der Behandlungsmasnahmen allerdings signifikant vom sehr heterogenen Verletzungsmuster abhangt, werden in dieser DRG okonomisch sehr unterschiedliche Falle zusammengefasst. Ziel dieser Arbeit war daher die Uberprufung der Kostendeckung fur die operative Behandlung von offenen Augenverletzungen an einer Universitats-Augenklinik. Die Leistungsdaten fur die DRG C01Z wurden fur die Jahre 2005 und 2006 uber die E1-Bogen nach §21 KHEntG zusammengefasst. Die Behandlungskosten wurden uber die Berechnung der OP-Fixkosten, der variablen OP-Kosten inklusive Personal und Material und der stationaren Kosten auf eine durchschnittliche OP heruntergebrochen. Im Untersuchungszeitraum wurden 180 offene Augenverletzungen von insgesamt 4721 stationaren Operationen behandelt. In 80 Fallen wurde eine Hornhaut-/Skleranaht (+Phako/IOL; n=10); (mittlere OP-Zeit: 67,81 min) durchgefuhrt. In 100 Fallen wurde eine Pars-plana-Vitrektomie (ppV) mit entsprechenden adjuvanten Masnahmen (mittlere OP-Zeit: 124,69 min) benotigt. Der OP-Fixkostenanteil pro OP belief sich auf 130,60 EUR; die variablen Kosten inklusive Personal und Material variierten zwischen durchschnittlich 570 EUR (Hornhaut-/Skleranaht ± 250 EUR fur Phako und IOL; n=10) und 1230 EUR fur die ppV. Kostentrachtige Adjuvanzien wie die Benutzung von Cerclage, Perfluorocarbonen, Gas und Silikonol sowie die kombinierte Phako ± IOL verursachten zusatzliche Kosten zwischen 51 und 250 EUR pro Zusatz (durchschnittlich 182 EUR) wobei mindestens zwei dieser Zusatze bei 50% und mindestens ein Zusatz bei 90% der ppVs benutzt wurde. Die stationaren Kosten beliefen sich bei einer mittleren Verweildauer von ca. 8 Tagen pro Fall auf 2184 EUR (Tagessatz 273 EUR). Die durchschnittlichen Gesamtkosten eines Falles differierten masgeblich fur die reine Naht-OP (2662 EUR, mittlere Verweildauer: 7,06 Tage) und ppVs (3712 EUR; mittlere Verweildauer: 8,62 Tage). Zusatzliche nicht gedeckte Kosten entstanden bei 20 Fallzusammenfuhrungen (11,1%) fur Reoperationen wahrend des stationaren Aufenthaltes. Die C01Z wurde im Erhebungszeitraum mit durchschnittlich 3205,96 EUR bei einem Relativgewicht von 1,177 und einer Baserate von 2723,79 EUR in Bayern vergutet. Damit sind die ppVs deutlich unterbezahlt und die reine Versorgung durch Naht ist deutlich uberbezahlt. Aufgrund der Inhomogenitat befurworten wir einen Split der C01Z fur penetrierende Augenverletzungen.

Purpose: Up to date several approaches have been undertaken to achieve an ‘easy-to-handle’ animal model of choroidal neovascularizations (CNVs) in rabbits; however, so far in none of the studies could healthy retinal tissue be maintained, which is mandatory to further investigate the effects of photodynamic therapy (PDT) or anti-vascular-endothelial-growth-factor treatments. It was our aim to reevaluate and verify the method of inducing experimental CNVs in rabbits using subretinally injected linoleic acid hydroperoxide (LHP) as proposed by Tamai et al. and to use it for experimental PDT. Material and Methods: In 33 eyes of Chinchilla breed rabbits LHP of two different concentrations (25 and 100 µg/50 µl) was injected into the subretinal space via a transvitreal approach under guidance of an operation microscope. Ophthalmoscopic and angiographic examinations were performed on days 3, 7, 14 and 28 after surgery. Preliminary PDT with different experimental parameter sets was performed in 3 eyes using the new photosensitizer Tookad. Results: Using LHP in the higher concentration, an angiographically determined CNV induction was observed in 27% of all injection sites (n = 34) on days 14 and 28 revealing early well-demarcated and progressive leakage. No CNV was detected at the lower LHP concentration (60 injection sites). Subretinal CNV was verified histologically revealing vessel formation above the retinal pigment epithelium level. Herein, a significant damage to the outer retinal layers was always observed; however, the general structure of the choriocapillary layer was maintained. Tookad PDT was clinically able to completely stop leakage in 1 case and reduce leakage in 2 cases. Histologically the choriocapillary layer was occluded. Conclusion: Subretinal injection of LHP induces angiographically well-demarcated classic CNVs in rabbits; however, the CNV rate was low, and histology revealed severe damage of the outer retinal layers but not of the choriocapillary layer, which is important for studying PDT interactions. Preliminary experimental PDT could clinically stop or reduce leakage from angiographic CNV. Due to the small CNV rate and the significant collateral retinal tissue damage, this model seems to be only of partial suitability for investigating new treatment modalities in CNV.

To carry out a prospective investigation of the functional and morphological outcome of idiopathic epiretinal membrane (IEM) surgery with or without the assistance of indocyanine green (ICG) in a randomised controlled clinical trial. Sixty patients who underwent vitrectomy with removal of IEM combined with cataract surgery were randomly allocated to two groups: 27 patients were operated on with ICG 0.1% in glucose 5%, 33 patients without ICG. Functional outcome was assessed 3-4 months postoperatively with improvement of best-corrected visual acuity (BCVA), Amsler grid test, and automated and kinetic perimetry. Postoperative residual or recurrent IEM was assessed with bio-microscopy, and macular oedema with optical coherence tomography (OCT). Improvement in BCVA was the main outcome measure. BCVA improved in 49 patients, remained unchanged in five and decreased in five. Improvement in BCVA and reduction of macular oedema were statistically significant within both groups (P

By definition, an electronic subretinal visual prosthesis requires the implantation of stimulation electrodes in the subretinal space of the eye. Polyimide film electrodes with flat contacts were implanted subretinally and used for electrical stimulation in acute experiments in anaesthetised domestic pigs. In two pigs, the film electrode was inserted through a sclerostomy into the vitreous cavity and, subsequently, via a retinotomy into the subretinal space around the posterior pole (ab interno approach). In three other pigs the sclera and pigment epithelium were opened for combined ab interno and transscleral positioning of the subretinal electrode. In all cases, perfluorocarbon liquid (PFCL) was used to establish a close contact between the film electrode and the outer retina. After cranial preparations of three pigs for epidural recording of visual cortex responses, retinal stimulation was performed in one pig with a film electrode implanted ab interno and in two pigs with film electrodes implanted by the ab interno and transscleral procedure. The five subretinal implantations were carried out successfully and each polyimide film electrode tip was positioned beneath the outer retina of the posterior pole. The retina was attached to the stimulation electrode in all cases. Epidural cortical responses to light and electrical stimulation were recorded in three experiments. Initial cortical responses to Ganzfeld light and to electrical stimuli occurred about 40 and 20 ms, respectively, after stimulation onset. The stimulation threshold was approximately 100 microA and, like the cortical response amplitudes, depended both on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. Our results in a domestic pig model demonstrate that polyimide film electrodes can be implanted subretinally and tested by recording cortical responses to electrical stimulation. These findings suggest that the domestic pig could be an appropriate animal model for basic testing of subretinal implants.

Purpose: Central serous chorioretinopathy (CSC) affects mostly young and middle-aged adults. Typically, a serous retinal detachment occurs with a focal leakage point in fluorescein angiography. Fundus autofluorescence (AF) is related to the lipofuscin within the retinal pigment epithelium (RPE). As CSC is thought to be associated with RPE disorders, AF measurements might be able to detect distinct changes within the RPE level. The purpose of this study was to compare AF patterns in acute and chronic-recurrent CSC and to evaluate the potential value of AF as a non-invasive monitoring tool. Methods: From 85 patients diagnosed with CSC (mean age 43 years), AF images were retrospectively evaluated and compared with angiographic and ophthalmoscopic findings. Fluorescein angiography and AF measurements were performed using a Heidelberg retina angiograph. Autofluorescence was excited at a wavelength of 488 nm and detected above 500 nm. Results: Acute CSC as determined by an acute decrease in visual acuity (VA) within the last 6 weeks, focal point leakage and neurosensory retinal detachment was diagnosed in 39 patients. In 36 of those patients (92%), a significantly decreased AF at the leakage point (72%) and/or decreased AF in the area of neurosensory detachment (77%) were observed. Regarding chronic-recurrent CSC as determined by a decrease in VA for longer than 6 weeks and mottled hyperfluorescent appearance in angiography, abnormalities in AF were observed in 44/46 patients (96%). In those patients, decreased or mottled AF was observed at the leakage point itself (76%), whereas significantly increased AF was seen in the area of residual neurosensory retinal detachment (85%). Conclusions: In acute CSC, decreased AF is presumably due to a blockage caused by oedema, whereas in chronic-recurrent forms, irregular and increased AF is observed, possibly reflecting reactive RPE changes secondary to RPE defects and neurosensory detachment. If these findings could be systematically underlined by prospective clinical studies, AF might be an interesting non-invasive tool for monitoring RPE changes in CSC and for performing differential diagnosis.

Non-invasive imaging of the retinal pigment epithelium (RPE) using autofluorescence became recently available with the introduction of confocal laser scanning ophthalmoscopes. Fundus autofluorescence is usually excited at a wavelength of 488nm and the emitted light is detected above 500nm. This intrinsic autofluorescence was shown to derive from the lipofuscin accumulating within the RPE either with age or also due to different hereditary or degenerative diseases of the macula as e.g. age-related macular degeneration. Since a variety of macular diseases correlate with distinct RPE changes, specific patterns of autofluoresce nce could be evaluated within the recent years for diagnostic and prognostic reasons in those RPE-related diseases. Moreover autofluorescence can also be regarded as a monitoring tool after therapeutic applications as macular surgery or laser treatment. Other new applications try to determine macular pigment density using autofluorescence or use it to evaluate oxygen-dependent cell metabolism. This review summarizes the recent findings of autofluoresce nt patterns in specific diseases and therapeutic approaches and emphasizes on the tremendous potential of this novel imaging method.

Following multiple promising investigations into restoration of vision in degenerative retinal disease by implantation of a sub- or epiretinal prosthesis, the step to clinical use in humans is impending. In this study we intended to establish optical coherence tomography (OCT) and fluorescein angiography (FA) first in research animals for noninvasive assessment of the condition of the posterior pole of eyes after intraocular implant surgery. Three adult cats that had undergone subretinal implant surgery were evaluated by OCT and FA between 1 and 470 days postoperatively. Eight adult cats served as control. In addition histology was performed. In all three cats OCT demonstrated stable positioning of the implants in the subretinal space during the complete examination period. Transient retinal edema was found in the early postoperative period but decreased during follow-up. The retina over the implants was well attached at all times in cats 1 and 2; however, in cat 3 localized retinal detachment was demonstrated. FA showed intact retinal vasculature over the subretinal implant in high detail without interference from choroidal background fluorescence. OCT and FA have been fruitfully applied to cats to assess the morphological and circulatory conditions of the neuroretina and of its interface with the subretinal implant. The techniques may therefore provide a tool for objective, noninvasive in vivo evaluation of eyes that have undergone subretinal implant surgery, both in research animals and in humans.

In hereditary retinal diseases photoreceptors progressively degenerate, often causing blindness without therapy being available. Newly developed subretinal implants can substitute functions of photoreceptors. Retina implant extraocular surgical technique relies strongly on cochlear-implant know-how. However, a completely new surgical approach providing safe handling of the photosensor array had to be developed. The Retina Implant Alpha IMS consisting of a subretinal microphotodiode array and cable linked to a cochlear-implant-like ceramic housing was introduced via a retroauricular incision through a subperiosteal tunnel above the zygoma into the orbit using a specially designed trocar. Implant housing was fixed in a bony bed within a tight subperiosteal pocket in all patients. Primary outcomes were patient short term safety as well as effectiveness. Nine patients participated in the first part of the multicenter trial and received the subretinal visual implant in one eye. In all cases microphotodiode array pull-through procedure and stable positioning were possible without affecting the device function. No intraoperative complications were encountered. The minimally invasive suprazygomatic tunneling technique for the sensor unit as well as a subperiosteal pocket fixation of the implant housing provides a safe extraocular implantation approach of a subretinal device with a transcutaneous extracorporeal power supply.

Hintergrund. Die konventionelle Behandlung des Zentralarterienverschlusses (ZAV) fuhrt in der Regel zu unbefriedigenden Ergebnissen. Eine invasive Therapiemoglichkeit stellt die selektive intraarterielle Fibrinolyse (IF) der A. ophthalmica dar. Zur Nutzen-Risiko-Abwagung beider Verfahren analysierten wir retrospektiv die Akten von 62 Patienten mit ZAV. Weiterhin wurde das Risikospektrum fur einen ZAV untersucht. Material und Methode. Krankenakten uber einen Zeitraum von 5 Jahren wurden ausgewertet und Patienten nach IF (n=17) und nach konventioneller Therapie (Drucksenkung, rheologische Masnahmen; n=45) hinsichtlich des Visus verglichen. Ausschlusskriterien fur die IF waren: Eintreffen spater als 8 h nach dem Verschlussereignis, medizinische Kontraindikationen wie Blutungsneigung, vorangegangene Operationen und hohes Alter (≥85 Jahre). Die IF wurde mit Urokinase (n=7) oder tPA (n=10) durchgefuhrt. Ergebnisse. Bei 22 von 62 Patienten (35%) wurde eine IF erwogen, wobei in funf Fallen aufgrund einer Gefasstenose darauf verzichtet werden musste, so dass insgesamt 17 Patienten eine IF erhielten. Bei 40 Patienten (65%) wurde primar keine IF aufgrund von Ausschlusskriterien angestrebt. Diese waren wie folgt: 47% (19/40) trafen spater als 8 h nach dem Verschlussereignis ein, 17% (7/40) stimmten der IF nicht zu, 15% (6/40) wiesen medizinische Kontraindikationen auf, 13% (5/40) waren uber 85 Jahre. Bei 8% (3/40) wurde ein IF nicht in Erwagung gezogen, da ein zilioretinales Gefas mit noch gutem Visus vorlag oder sich wahrend der Untersuchung ein spontaner Visusanstieg ergab. Vier von 17 Patienten mit IF zeigten eine Visusverbesserung um mindestens zwei Zeilen, 12/17 hatten keine Veranderung, und 1/17 wies eine Verschlechterung um mindestens zwei Zeilen auf. Von den konservativ behandelten Patienten erreichten 16/45 eine Visusverbesserung um mindestens zwei Zeilen, bei 29/45 ergab sich keine Visusanderung. Bei drei Patienten mit IF musste aufgrund einer akuten Halbseitensymptomatik die Therapie abgebrochen werden. Haufigster Risikofaktor fur den ZAV war der systemische Hypertonus bei 32% aller Patienten gefolgt vom Nikotinabusus (16%). Schlussfolgerung. Insgesamt zeigte sich, dass ein Grosteil der Patienten mit ZAV fur eine eventuelle IF als Therapie der Wahl zu spat die Klinik erreicht. Bezogen auf den Visus ergab sich jedoch statistisch kein Unterschied zwischen IF und konventioneller Behandlung. Aufgrund des Komplikationsrisikos bei der IF sollte eine prospektive Studie den Stellenwert der IF festlegen. Konsequente Blutdruckeinstellung ist als notwendige Prophylaxe gegen einen ZAV anzusehen.

Es wird eine Ubersicht uber den Stand der Entwicklungen eines subretinalen, elektronischen Mikrophotodioden-Arrays gegeben, mit dem degenerierte Photorezeptoren ersetzt werden konnen. Verschiedene Prototypen wurden entwickelt, getestet und bei verschiedenen Versuchstieren bis zur Dauer von 18 Monaten implantiert. Die Tatsache, dass mit subretinalen Elektroden elektrische Antworten vom visuellen Kortex von Schweinen abgeleitet werden konnen und Antworten auch in vitro in Netzhauten von Ratten mit Netzhautdegenerationen nachweisbar sind, zeigt die Sinnhaftigkeit dieses Ansatzes. Allerdings sind noch wichtige Fragen der Biokompatibilitat, der Langzeitstabilitat und der Art des vermittelbaren Bildeindrucks zu bearbeiten, bevor an einen Einsatz beim Menschen zu denken ist.

Hintergrund: Eine isolierte Aspergillose des Sinus sphenoidalis ist eine schwierige Diagnose, da die oftmals missgedeuteten Beschwerden und die klinischen Symptome dieser seltenen Erkrankung sich erst spat entwickeln und den Patienten zuerst auch zum Augenarzt fuhren konnen. Da bei den in der Regel immuninkompetenten Patienten auch eine Lebensbedrohung mit haufig letalem Ausgang besteht, ist eine dringende Abklarung und Behandlung indiziert. Kasuistik: Wir berichten uber einen immunkompetenten Patienten, bei dem nach externer Voroperation einer Mukozele eine Aspergillusinfektion der Nasennebenhohlen und Orbita zu einem akuten einseitigen Visus- und Gesichtsfeldverlust fuhrte (Visus 0,1). Eine sofortige antimykotische systemische Therapie wurde eingeleitet und die Orbita und der Canalis opticus operativ von der Mykose saniert. Dabei zeigte sich der N. opticus in der Orbitaspitze zirkular durch den Pilz ummauert. Nach der Operation kam es innerhalb von 2 Wochen langsam zu einer vollstandigen visuellen Rehabilitation (Visus 1,0) und Normalisierung des Gesichtsfeldes seit nun uber einem Jahr. Schlussfolgerung: Der Leitbefund eines in der Anamnese einseitigen Visusverlustes und HNO-arztliche Voroperationen in Zusammenhang mit dem Symptom eines persistierenden Kopfschmerzes kann aus augenarztlicher Sicht den Verdacht auf eine Aspergillusinfektion nahe legen. Die richtige Diagnose bei dieser seltenen Erkrankung – insbesondere bei immunkompetenten Patienten – sollte moglichst schnell gestellt sein, um einen irreversiblen Sehverlust vermeiden zu konnen und bei bereits fortgeschrittenem Stadium der Erkrankung die ernste Lebensbedrohung des Patienten durch Pilzmeningitis zu verhindern.

Background Subretinal hemorrhage in age related macular degeneration (AMD) usually causes acute visual loss and is associated with poor visual prognosis. In order to prevent retinal damage and to perform laser treatment of the underlying choroidal neovascularization (CNV) the subretinal hemorrhage has to be removed from the macular region. This could be achieved by intravitreal injection of tissue plasminogen activator (tPA) and gas. Patients and methods In 8 consecutive patients, suffering from a massive macular hemorrhage (duration of visual problems: mean 9 days), tissue plasminogen activator (tPA) (40 micrograms in 400 microliters BSS) and SF6-gas (0.75 ml) was transsclerally injected into the vitreous cavity to achieve liquification and displacement of the hemorrhage. Results In all patients liquification and displacement of the hemorrhage out of the macular region was achieved during follow up. During the first week after operation a significant increase of visual acuity was noticed in all patients, however ophthalmoscopically there was just little reduction of the hemorrhage in the foveolar area. After successful removal of the blood the choroidal neovascularization was treated successfully by laser coagulation in one patient. No laser treatment was performed in the other patients because of the subfoveal location of the neovascularisation or because of disciform scar. Visual acuity increased 4 lines after surgery. In one case the procedure was complicated by a persistent vitreous hemorrhage and vitrectomy had to be performed in another patient due to an endophthalmitis. Conclusion Intravitreal injection of tPA assisted gas displacement of subretinal hemorrhage due to AMD leads to a significant increase of visual acuity during the first week after operation. Although a nearly complete removal of the hemorrhage out of the macular area could be achieved, it was difficult to differentiate this from the spontaneous course. Laser photocoagulation could be performed in only few cases.

Background The circumscript cutaneous sclerosis is an inflammato-edematous erythema of the skin, usually leading to a plaque-like sclerosis and cutaneous atrophy. The etiology of this disease remains unknown, but some authors presume a systemic infection with Borrelia burgdorferi as the underlying pathological condition. Patient We present a case of a 66-year-old male patient who suffered from episcleritis of his left eye. Funduscopy showed an unilateral papillary edema. Visual acuity was 1.0. The patient had multiple erythemata of the skin of the body-trunk and the arms. On histological examination the lesions were compatible with circumscript sclerosis. Neurological examination was normal. Brain imaging (MRI), CSF examination and serology showed no pathological findings, although the patient presented with raised antibodies against Borrelia burgdorferi (IgG positive, IGM negative). Intravenous antibiotic treatment and topical steroids for three weeks resulted in a complete recovery of the scleritis, but had no effect on the papillary edema. Conclusion Inflammatory pathological findings of the eye can be associated with circumscript sclerosis, a disease, that is normally limited to the skin. The pathological mechanism remains unclear. The presumption of an underlying borreliosis could not be confirmed in this case.

Purpose An active microelectronic subretinal implant, developed to replace the photoreceptive function in hereditary degenerations of the outer retina, has been applied in a pilot and clinical study in patients with end-stage retinal degeneration. Methods The study population comprised 20 blind patients, all of whom lost vision as result of a hereditary retinal disease. An active visual implant was placed surgically within the subretinal space of each patient: subfoveal placement in eight patients (group 1) and parafoveal placement in 12 (group 2). Standardized low-vision tests, including light perception, light localization, movement detection, grating acuity, and visual acuity by Landolt C-rings, were used under masked, randomized implant-OFF and implant-ON conditions. For the chip-mediated vision functional results of both subject groups were compared. Results Three of 20 patients were excluded from analysis because of surgical or technical implant issues. Among patients with nonfoveal placement of the implant, 80% could perceive light, 10% recognized location, and 10% correctly distinguished stripe patterns up to a resolution of 0.33 cycles/degree. No nonfoveal placement patient passed the motion or Landolt C-ring tests. When the implant was placed subfoveally, 100% of patients could perceive light and determine light localization, 75% could resolve motion up to 35°/s, 88% correctly distinguished stripe patterns up to a resolution of 3.3 cycles/degree, and 38% passed a Landolt C-ring test with a decimal visual acuity of up to 20/546 (logMAR 1.43). Conclusions Subfoveal placement of active subretinal visual implants allows superior measurable outcomes compared to para- or nonfoveal placement locations. (ClinicalTrials.gov numbers, NCT01024803, NCT00515814.).

This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm 2 chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s −1 ), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037 or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly ( n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implant's power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.

Die Anwendung von 5-Fluorouracil (5-FU) zur Reduktion der Vernarbungstendenz bei filtrierend Glaukomoperationen zeigte bei subkonjunktivaler Gabe eine Erhohung der Erfolgsrate der filtrierenden Eingriffe. Seit dem In-vitro-Nachweis einer antiproliferativen Wirkungsdauer von 36 Tagen bei 1maliger Applikation von 5-FU wurde 5-FU auch intraoperativ angewandt. Die vorliegende Studie untersuchte den Effekt von intraoperativ appliziertem 5-FU an einem Kollektiv von 13 Glaukomaugen, die kein erhohtes Vernarbungsrisiko aufwiesen. Das Vergleichskollektiv wurde nach Alter, Diagnose, Geschlecht und Glaukomschaden ausgesucht. Der postoperative mittlere Druckverlauf war bei der Anwendung von 5 FU mit 7,8 mmHg am 4. Tag si-gnifikant (p=0,005) (power 0,80) niedriger als im Vergleichskollektiv (12,6 mmHg). Nach 1 Woche last sich nur noch ein Trend mit p=0,16 von 2 mmHg niedrigeren Druckwerten nachweisen. Im weiteren Verlauf zeigten sich keine signifikanten Druckunterschiede. Nebenwirkungen, wie korneale Komplikationen, intraokulare Reizzustande, wurden bei der direkten intraoperativen 5-FU-Gabe nicht vermehrt beobachtet. Jedoch ist ein Fall einer persistierenden Hypotonie in der 5-FU-Gruppe aufgetreten. Der kurzfristig deutliche postoperative Druckabfall last neben dem antiproliferativen Effekt des 5-FU auf direkt toxische Wirkungsweisen des 5-FU als Ursache schliesen.

Purpose Restitution of vision in blind Retinitis Pigmentosa patients by the new wireless implant Alpha-IMS (Retina Implant AG, Tubingen, Germany). Methods Each of the 1500 subfoveal photodiodes within an 11 by 11 deg field controls an amplifier that ejects light evoked currents onto bipolar cells via TiN electrodes (Zrenner et al. Proc. R. Soc. B 2011, 278: 1489ff). Power and control signals are transmitted transdermally via retroauricular inductive coils connected to a subdermal cable to the eye. Results Ten patients received implants since 2010 (average age 46±84). In 8 patients the chip was at the desired subfoveal position; in 2 patients slightly parafoveal. All patients were able to perform the function tests except one due to loss of inner retina function after surgery. Results in all other patients were: light perception 9/9; light localization 8/9; motion recognition 5/9; grating resolution 8/9 (up to 3,3 cycle/degree); Landolt C rings 3/9 (up to 0,036); recognition of geometric objects 8/9; recognition of objects in table setup 8/9; letter reading 4/9; clock hands reading 3/9; grey scale differentiation 6/9; improved outdoor mobility 5/9. Patients` experiences: recognition of unknown objects, facial or clothes’ characteristics, moving objects in nature and traffic, small objects (glasses, telephone, doors, door handles, washing basin, dices). Conclusion The wireless Alpha-IMS implant can restore useful visual abilities in blind RP-patients. Subretinal surgery for positioning chips subfoveally is safe and the multicenter part of the study has been started in Oxford, London and Hongkong. Commercial interest

Purpose To investigate visual perception of previously blind retinitis pigmentosa (RP) patients using electronic subretinal implants. Methods The new Alpha IMS chip (Retina Implant AG) with its 1500 photodiodes, amplifiers and electrodes powered wirelessly via a subdermal coil was implanted subretinally in 7 retinitis pigmentosa patients for indoor and outdoor use. Results VA was up to 21/1000 within a field of 11° by 11° (see previous pilot study http://rspb.royalsocietypublishing.org/content/early/2010/11/01/rspb.2010.1747). A) Near vision: Localizing, cutlery and tableware, plates and content in 4AFC mode and in restaurants, facial characteristics of persons, items on working desk. B) Far vision: Recognizing clouds, clothes of people, borders of cars by metallic reflections, discerning smaller from larger persons. C) Spatial resolution: Position of clock hands, stripe patterns up to approx. 0.33 – 0.44 cpd, reading letters 4 to 8 cm high, localization and recognition of square, round or rectangular objects . D) Contrast: Differentiation of 7 to 10 shades of grey; increased sensitivity for infrared radiation. E) Motion: Hand movement, walking direction of a goose, circumvention of obstacles. F) Eye-hand coordination: Pointing at objects and moving them. Conclusion Subretinal Alpha IMS implants allow RP- patients within few days of exercising to localize objects and to perform visuomotor tasks for improved orientation and mobility. This device thereby can provide considerable support to blind RP patients in mastering tasks of daily life, indoor and outdoor, as shown in an ongoing clinical study. Commercial interest

Our group has developed a subretinal microphotodiode array for restoration of vision. In a clinical pilot study the array has been implanted in 11 patients suffering from photoreceptor degenerations. Here we present promising results from some of those patients where the retinal tissue above the chip was functional and the implant fulfilled its expected function. A spatial resolution of approximately 0.3 cycles/degree could be achieved with fine stripe patterns. In one subject where the implant had been placed directly under the macular region of the retina a visual acuity of 20/1000 could be measured. Artificially restored visual acuity of this quality has not been reported previously. Finally, we present images illustrating an approximation of how the visual perceptions might have appeared to the subjects, based on a mathematical model and patient reports.

Two patients carrying an active subretinal implant with extra-ocular parts were examined by high-resolution CT. Cranial scans were acquired in the primary position and in eight additional directions of gaze with eyes open and closed to demonstrate the mobility of the eyeball and the implant within the orbital cavity. Three-dimensional images were constructed to visualise the path of the implant from the retro-auricular space around the lateral orbital rim through the orbit and within the subretinal space up to the device's final para-foveal position. Images were obtainable in high quality, resulting in three-dimensional models illustrating all parts of the implant including the micro-photodiode array at the tip in the subretinal space. The implant followed eye movements in all directions of gaze; eye movements were only minimally restricted as described in previous publications. Since all, except intra-ocular, parts of the implant evade direct examination, CT can be useful to assess the technical integrity and the biocompatibility and biostability of retinal implants.

To compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas.Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea.Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A.ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.

Purpose Restoration of letter reading and stripe pattern recognition in blind RP patients by placing subretinal implants transchoroidally near the macula, consisting of two arrays: 4x4 electrodes controlled retroauricularly via a subdermal line for direct stimulation (“DS array”) and a "chip" (3x3x0,1 mm),1500 electrodes. Methods Letters and stripe pattern were presented to 3 patients via the light sensitive chip – by patterns steadily presented at a screen. On the DS array the sensation evoked by each individual pulse consists of whitish round dot, clearly separated from its neighbor. Patterns consisting of such 4 x 4 dots correspond to letters of approximately 5 cm diameter presented at 60 cm distance. Results Pat.1 correctly (20/24) recognized the direction of the letter “U”, presented with the opening in four different directions (DS array). Pat.2 correctly (12/12) differentiated letters via DS array (e.g. COIL). With the light sensitive chip, he correctly (22/24) differentiated letters (e.g. LITZ; 8,5 cm high, 1.7 cm line width) steadily presented on a screen at 62 cm distance Pat.3 recognized (15/20 correct, 4AFC) the direction of lines or stripe patterns with the chip, as did Pat.1 (11/14, 2AFC) and Pat.2 (11/12 4AFC) up to 0.35 cycles/deg. Conclusion Active subretinal multielectrode implants with currents close to produce retinotopically correct patterns that allow for the first time recognition of individual letters and stripe patterns up to 0.35 cycles/deg clearly supporting the feasibility of light sensitive subretinal multi-electrode devices for restoration of useful vision.

Background: Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. Methods: Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. Results: All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. Conclusion: The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.