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Zusammenfassung Hintergrund Das Retina.net ROP-Register erhebt Daten von Kindern, die eine seltene behandlungsbedürftige Frühgeborenenretinopathie (Retinopathy of Prematurity, ROP) entwickeln. Ziel dieser Auswertung ist die Untersuchung der Daten zur behandlungsbedürftigen ROP, Epidemiologie, Therapie und deren Änderungen über einen Zeitraum von 15 Jahren an der Medizinischen Hochschule Hannover. Methoden Analyse der Daten der therapiebedürftigen Fälle der ROP eines Zentrums für die Geburtsjahre 2001 bis 2016 (Therapie in 2002 bis 2017) als Gesamtzeitraum und in 5 Abschnitten. Ergebnisse Es wurden 65 Kinder behandelt (23 weiblich), davon wurden 11 (16,9 %) extern auf ROP gescreent und zur ROP-Behandlung zugewiesen. Für den Zeitraum 2006 bis 2016 lag die Inzidenz der behandlungsbedürftigen ROP unter den gescreenten Kindern bei 4,1 %. Das mittlere Gestationsalter betrug 25,7 Schwangerschaftswochen (SSW) (Standardabweichung [SA] = 1,8), das Geburtsgewicht 763 g (SA = 235), das postmenstruelle Alter bei Behandlung 38,2 Wochen (SA = 3,2), das postnatale Alter 12,4 Wochen (SA = 3,2). Über die Zeit zeigte sich kein signifikanter Unterschied der demografischen Parameter. Am häufigsten (57 Augen bei 31 Kindern) wurde eine Zone II, 3+-Erkrankung behandelt; 58 Kinder erhielten eine Laserkoagulation (N = 114 Augen), 7 Kinder bilateral eine Anti-VEGF-Therapie (Bevacizumab) (N = 14 Augen), welche ab 2014 eingesetzt wurde. Eine Wiederbehandlung bei Wiederaufflammen der behandlungsbedürftigen ROP war in einem Fall nach initialer Laserbehandlung notwendig. Kinder mit behandlungsbedürftiger ROP zeigten häufig neonatologische Komorbiditäten, in mehr als 90 % Beatmung, bronchopulmonale Dysplasie und erhielten Transfusionen. Schlussfolgerung Dies ist die erste monozentrische Auswertung über 15 Jahre im Rahmen des Retina.net ROP-Registers. Ab 2014 sehen wir einen Wechsel von der Laserkoagulation zur Anti-VEGF-Therapie (Bevacizumab), während im betrachteten Kollektiv die demografischen Daten und Behandlungsparameter weitgehend konstant waren.

Background: Patients with Sjögren’s syndrome and polyneuropathy more frequently develop cranial nerve affection when compared to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We therefore aimed to analyze trigeminal corneal nerve fibre characteristics in both patient groups. Methods: A total of 26 patients with Sjögren’s syndrome associated neuropathy and 29 patients with CIDP were recruited at our university hospital and compared to 6 healthy controls. Dry eye symptoms and signs were assessed via clinical examination and the Ocular Disease Surface Index questionnaire. Trigeminal corneal nerve fibres were analyzed via corneal confocal microscopy (CCM) as a non-invasive in vivo microscopy. Results: CCM revealed significantly reduced corneal nerve fibre density and corneal nerve fibre main branch density in the Neuro-Sjögren group when compared with healthy controls. There were no significant group differences between the Neuro-Sjögren and the CIDP group for any of the microscopic parameters. Dry eye assessment showed similarly reduced scores for both patient groups, while healthy controls showed better results for objective dry eye signs. There was no correlation between microscopic parameters of the corneal confocal microscopy and parameters of dry eye assessment. Conclusions: Our data revealed trigeminal corneal nerve affection in patients with neuropathy associated with Sjögren’s syndrome and patients with CIDP detected by CCM. No difference was found between both neuropathy groups indicating that CCM is not able to distinguish between both entities.

Purpose Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy. Material and methods This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®). Results Mean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42–191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22–217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88–218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures. Conclusion Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.

Purpose Optic disc pits (ODPs) are rare congenital anomalies. Several patients develop optic disc pit maculopathy (ODP-M): visual impairment caused by intra- and/or subretinal fluid. Treatment mode remains controversial. This study was designed to investigate the effectiveness of pars plana vitrectomy (PPV) and gas tamponade with or without internal limiting membrane (ILM)-peeling in improving visual acuity and reducing subretinal fluid in ODP-M patients. Methods We retrospectively reviewed the charts of 16 patients who underwent surgery for ODP-M from 2002–2015. Six patients underwent PPV with gas tamponade (group 1); ten patients additionally received ILM-peeling (group 2). Pre- and postoperative visual acuity and central retinal thickness (CRT) were compared between groups, as well as retinal morphology and the number of secondary vitrectomies and complications. Results Median visual acuity improved by 2 ETDRS lines in both groups (p = 0.713, Mann–Whitney U test). Median CRT decreased by 426.5 µm and 460 µm (p = 0.931). One patient in group 1 underwent repeat vitrectomy for persistent retinoschisis. Three patients in group 2 required repeat vitrectomy: two to treat a macular hole, one for peripheral retinal holes with retinal detachment. Conclusion In our cohort, PPV with gas tamponade proved to be an effective first-line treatment for ODP-M. Additional ILM-peeling did not give a significant benefit in this study.

Purpose To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma. Methods Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging. Results In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017). Conclusion There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.

Purpose: To compare ischemia-related clinical outcomes in patients treated with either ranibizumab pro re nata (PRN) or single dexamethasone implant in the Branch Retinal Vein Occlusion (COMRADE-B)...

Retinal artery occlusion (RAO) represents a limiting visual perception for affected patients. In all efforts to improve function it must not be forgotten that in the vast majority of cases the cause is one or more severe vascular or cardiac diseases, which can cause RAO just as ischemic stroke and can also be life-threatening.The aim of this article is to present the available literature and to explain the importance of an intensive neurological internal medical clarification in RAO patients.Although cardiovascular diseases are already known in most patients at the onset of an RAO, further risk factors are detected in almost 80% of cases. Therefore, and because of the high risk for recurrent thromboembolism, immediate and standardized neurological internal medical clarification of the cause is urgently recommended after an acute RAO in the context of an inpatient stay.HINTERGRUND: Der retinale Arterienverschluss (RAV) bedeutet für die betroffenen Patienten eine einschränkende Sehwahrnehmung. Bei allen Bemühungen um eine Funktionsverbesserung darf aber nicht vergessen werden, dass die Ursache in den allermeisten Fällen eine oder mehrere schwerwiegende vaskuläre oder kardiale Erkrankungen darstellen, die gleichermaßen RAV wie Schlaganfälle bedingen und auch lebensbedrohlich sein können. ZIEL: In diesem Beitrag soll die verfügbare Literatur dargelegt und die Bedeutung der intensiven neurologisch-internistischen Abklärung bei RAV-Patienten erklärt werden.Obwohl bei den meisten Patienten bereits kardiovaskuläre Erkrankungen beim Eintreten eines RAV bekannt sind, werden bei fast 80 % weitere Risikofaktoren entdeckt. Deshalb und aufgrund des hohen Risikos für thromboembolische Folgeereignisse ist die umgehende und standardisierte neurologisch-internistische Ursachenabklärung nach einem akuten RAV im Rahmen eines stationären Aufenthalts dringend anzuraten.

Summary Background The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical trial. Methods This randomised, placebo-controlled, double-blind phase 3 trial, conducted at 12 tertiary referral centres in Germany, included participants aged 18–50 years, within 10 days of onset of unilateral optic neuritis, with visual acuity of 0·5 or less, and without a previous diagnosis of multiple sclerosis. Participants were randomly assigned (1:1) to receive either 33 000 IU erythropoietin or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1000 mg per day). Block randomisation was performed by the trial statistician using an SAS code that generated randomly varying block sizes, stratified by study site and distributed using sealed envelopes. All trial participants and all study staff were masked to treatment assignment, except the trial pharmacist. The first primary outcome was atrophy of the peripapillary retinal nerve fibre layer (pRNFL), measured by optic coherence tomography (OCT) as the difference in pRNFL thickness between the affected eye at week 26 and the unaffected eye at baseline. The second primary outcome was low contrast letter acuity at week 26, measured as the 2·5% Sloan chart score of the affected eye. Analysis was performed in the full analysis set of all randomised participants for whom treatment was started and at least one follow-up OCT measurement was available. Safety was analysed in all patients who received at least one dose of the trial medication. This trial is registered at ClinicalTrials.gov, NCT01962571. Findings 108 participants were enrolled between Nov 25, 2014, and Oct 9, 2017, of whom 55 were assigned to erythropoietin and 53 to placebo. Five patients were excluded from the primary analysis due to not receiving the allocated medication, withdrawn consent, revised diagnosis, or loss to follow-up, yielding a full analysis set of 52 patients in the erythropoietin group and 51 in the placebo group. Mean pRNFL atrophy was 15·93 μm (SD 14·91) in the erythropoietin group and 14·65 μm (15·60) in the placebo group (adjusted mean treatment difference 1·02 μm; 95% CI −5·51 to 7·55; p=0·76). Mean low contrast letter acuity scores were 49·60 (21·31) in the erythropoietin group and 49·06 (21·93) in the placebo group (adjusted mean treatment difference −4·03; −13·06 to 5·01). Adverse events occurred in 43 (81%) participants in the erythropoietin group and in 42 (81%) in the placebo group. The most common adverse event was headache, occuring in 15 (28%) patients in the erythropoietin group and 13 (25%) patients in the placebo group. Serious adverse events occurred in eight (15%) participants in the erythropoietin and in four (8%) in the placebo group. One patient (2%) in the erythropoietin group developed a venous sinus thrombosis, which was treated with anticoagulants and resolved without sequelae. Interpretation Erythropoietin as an adjunct to corticosteroids conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. Future research could focus on modified erythropoietin administration, assess its efficacy independent of corticosteroids, and investigate whether it affects the conversion of optic neuritis to multiple sclerosis. Funding German Federal Ministry of Education and Research (BMBF).

The treatment of macular edema with intravitreal injections has revolutionized the treatment of associated diseases in ophthalmology. However, with a few exceptions, this is a chronic treatment where patients require many injections and usually need to stay in treatment for years. Patient adherence and control of patient flow are critical to treatment success. In this manuscript, we describe the development of a patient-oriented organization management for intravitreal injections in a university hospital.In 2015, the intravitreal treatment in our clinic was switched to the treat-and-extend regime. At the same time, the optimization of the previous organizational processes in perioperative management was evaluated. For the period 2015 to 2018, we analyzed and gradually optimized the procedures of our intravitreal injection therapy in a survey with a specialized service provider.Through the analysis of the original processes, the patient appointment was optimized, work processes were summarized, spatially reorganized and there was only a slight increase in the number of staff involved compared with the significant increase in the number of injections. Through these measures, the total in-hospital-time of the patients could be drastically reduced and at the same time the number of patients on one operation day could be multiplied.In the context of chronic treatment with intravitreal injections, the care of an increased number of patients is a logistical challenge. By optimizing processes, existing resources can be better used to meet the increased demands. An optimized system offers the patient greater adherence and a better visual outcome largely independent of the medication used.Die Behandlung eines Makulaödems mittels intravitrealer Injektionen hat die Behandlung der assoziierten Krankheitsbilder in der Augenheilkunde revolutioniert. Abgesehen von einigen wenigen Ausnahmen handelt es sich jedoch um eine chronische Behandlung, bei der die Patienten viele Injektionen benötigen und i. d. R. über Jahre in Behandlung bleiben müssen. Die Adhärenz der Patienten und die Steuerung des Patientenflusses ist mit entscheidend für den Behandlungserfolg. In diesem Manuskript beschreiben wir die Entwicklung eines patientennahen Organisationsmanagements für intravitreale Injektionen in einer Universitätsklinik.Im Jahr 2015 wurde in unserer Klinik die intravitreale Behandlung auf das Treat-and-Extend-Regime umgestellt. Zugleich erfolgte die Evaluation der Optimierung der bisherigen Organisationsabläufe im perioperativen Management. Für den Zeitraum 2015 bis 2018 haben wir im Rahmen einer Erhebung mit einem spezialisierten Dienstleister die Abläufe unserer intravitrealen Injektionstherapie analysiert und schrittweise optimiert.Durch die Analyse der ursprünglichen Abläufe wurde die Patienteneinbestellung optimiert, Arbeitsabläufe wurden zusammengefasst sowie räumlich neu geordnet und es fand eine verglichen mit der deutlichen Erhöhung der Injektionszahlen nur geringfügige Erhöhung der beteiligten Mitarbeiterzahl statt. Durch diese Maßnahmen konnte sowohl die Gesamtaufenthaltszeit der Patienten deutlich reduziert werden als auch zugleich die Patientenzahl bei guter Adhärenz und guten Visusergebnissen an einem Operationstag vervielfacht werden.Im Rahmen der chronischen Behandlung mittels intravitrealer Injektionen ist die Versorgung einer gestiegenen Anzahl an Patienten eine logistische Herausforderung. Durch Optimierung von Abläufen können vorhandene Ressourcen besser genutzt werden, um den gestiegenen Anforderungen gerecht zu werden. Ein optimiertes System bietet für den Patienten eine höhere Adhärenz und ein besseres Visusergebnis weitgehend unabhängig von dem verwendeten Medikament.

In klinischen Studien bestehen im Vergleich zur klinischen Routine hohere Anforderungen, was einen zeitlichen Mehraufwand bedingt. Ziel dieser Arbeit ist die vollumfangliche Zeiterfassung an den deutschen ophthalmologischen Studienzentren. Mit 3 Fragebogen wurden bei den Mitgliedern der „Arbeitsgemeinschaft DOG Klinische Studienzentren“ der geschatzte Zeitaufwand fur die studienbezogenen Tatigkeiten, fur die Administration und prospektiv die tatsachliche Verwendung der Arbeitszeit abgefragt. Fur Letzteres wurde von jedem Mitarbeiter 3 Wochen lang zu jeder vollen Stunde ein Fragebogen ausgefullt („work sampling“). Die Fragebogen wurden von 9 der 11 angefragten Zentren ausgefullt. Insgesamt wurden 5504 Arbeitsstunden protokolliert. An einem durchschnittlichen Arbeitstag betrug der mittlere Aufwand fur Dokumentation und Administration jeweils 4 h. Signifikant waren auch operative Eingriffe (2,8 h), augenarztliche Untersuchungen (2,5 h) und Einwilligungsgesprache (1,5 h). Die protokollierte Dauer von Visusmessung, Einwilligung und Dokumentationen passte gut zu den Angaben aus den Fragebogen. Operative Eingriffe, augenarztliche Untersuchungen und die Handhabung von Bioproben wurden in der Dauer unterschatzt. Ein erheblicher Teil des Zeitaufwandes fallt fur Dokumentation an. Administrative Aufgaben sind ahnlich bedeutsam. Der uberraschend hohe Zeitbedarf fur operative Eingriffe, Untersuchungen und Handhabung von Bioproben resultiert wahrscheinlich aus Tatigkeiten zur Vor- und Nachbereitung, was im Kontext einer Vollkostenrechnung berucksichtigt werden muss. Viele administrative Tatigkeiten lassen sich zudem nicht ausreichend uber „case payments“ abbilden, sodass Zusatzvergutungen fur den kostendeckenden Betrieb eines ophthalmologischen Studienzentrums erforderlich sind.

ZusammenfassungNach neuesten Erkenntnissen ist ein Makulaödem infolge eines retinalen Venenverschlusses am besten mit einer zeitnahen intravitrealen Anti-VEGF-Therapie (Aflibercept, Bevacizumab [off label], Ranibizumab) sicher und effektiv behandelbar. Nach einem anfänglichen Upload von monatlich 3 Injektionen Anti-VEGF sollte in regelmäßigen Kontrollen vor allem OCT-basiert (bevorzugt gegenüber visusbasiert) über eine erneute Injektion entschieden werden. Nach anfänglichen monatlichen Injektionen haben sich derzeit vor allem das „Pro-re-nata“- (PRN) und das „Treat-and-Extend“-Schema in Bezug auf den weiteren Therapieverlauf durchgesetzt. Unter Beachtung des Nebenwirkungsspektrums (insbesondere Kataraktprogression, Augeninnendruckerhöhung) kann auch eine intravitreale Therapie mit einem Dexamethason-Implantat sinnvoll sein. Die Prognose bez. Visus und Rückgang des Makulaödems hängt von einem frühen Behandlungsbeginn mit konsequenter Therapiefortführung ab. Vor Behandlungsbeginn sowie im Verlauf ist eine Fluoresceinangiografie nötig, um ischämische Netzhautareale zu detektieren. Es gibt Hinweise, dass eine frühe gezielte Laserkoagulation ischämischer Netzhautareale die Frequenz der nötigen Injektionen senkt und zu einem besseren Ansprechen des Ödems auf die Therapie führt. Bei signifikanter retinaler Ischämie, die in der Folge zu Proliferationen, Rubeosis iridis und einem Sekundärglaukom führen kann, ist eine Laserbehandlung unumgänglich.

Patients suffering from type 2 diabetes are at an increased risk of developing classical microvascular complications such as retinopathy, neuropathy, and nephropathy, which represent a significant health burden. Tight control of blood glucose, blood pressure, and serum cholesterol reduce the risk of microvascular complications but effective pharmacologically targeted treatment options for the treatment and prevention of diabetic microangiopathy are still lacking. Pharmacological inhibition of sodium glucose cotransporter 2 (SGLT2) might have the potential to directly protect against microvascular complications and could represent a potential treatment option. Randomized controlled clinical proof of concept trials are needed to investigate a potential central role of SGLT2 inhibitors in the prevention of diabetic microangiopathy and its classical clinical complications of retinopathy, neuropathy, and nephropathy.

ZusammenfassungDas Ziel dieses Artikels ist es, einen Überblick zu geben über verschiedene Strategien zur Verwendung von PRN- und T&E-Therapieschemata (PRN: pro re nata; T&E: treat and extend) mit intravitrealen Anti-VEGF-Medikamenten (Bevacizumab, Ranibizumab oder Aflibercept) bei Patienten mit Netzhauterkrankungen wie neovaskulärer AMD, diabetischem Makulaödem und Makulaödem aufgrund von retinalen Venenverschlüssen. Der Schwerpunkt liegt dabei darauf, die Wirksamkeit und die Visusergebnisse des PRN- und des T&E-Regimes in Korrelation mit den wichtigsten Zulassungsstudien und Studien basierend auf den derzeit verfügbaren Daten vorzulegen. Wir diskutieren auch die Vor- und Nachteile der beiden Therapieregimes sowie die Überwachung und Behandlung der Krankheitsaktivität einschließlich der Behandlungsintervalle und Injektionsfrequenz. Derzeit gibt es ein zunehmendes Interesse, ein Regime zu etablieren, das die besten Visusergebnisse bei reduzierter Injektionsfrequenz und konsekutiv geringerer Belastung der Patienten durch individualisierte Behandlungsintervalle mit Minimierung der Anzahl der Klinikbesuche und der entstehenden Kosten bietet. Studien haben gezeigt, dass das PRN-Regime im realen Klinikalltag keine optimalen Visusergebnisse liefert. PRN erfordert häufige Arztbesuche, um den Krankheitsstatus zu kontrollieren und intravitreale Behandlung bei Bedarf reaktiv zu indizieren. Individualisierte T&E-Regimes können das Visusergebnis mit signifikant weniger Kontrolluntersuchungen verbessern im Gegensatz zu Therapieschemata mit einer monatlichen Applikation oder einem PRN-Regime.

To compare the efficacy and safety of the European labels of ranibizumab 0.5 mg vs dexamethasone 0.7 mg in patients with macular edema secondary to central retinal vein occlusion (CRVO).Phase IIIb, multicenter, double-masked, randomized clinical trial.Patients were randomized (1:1) to receive either monthly ranibizumab followed by pro re nata (PRN) treatment (n = 124) or 1 sustained-release dexamethasone implant followed by PRN sham injections (n = 119). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean change in BCVA, and adverse events (AEs).Of 243 patients, 185 (76.1%) completed the study. No difference was observed in BCVA between ranibizumab and dexamethasone at months 1 and 2. From month 3 to month 6, there was significant difference in BCVA gains in favor of ranibizumab. At month 6, mean average BCVA gain was significantly higher with ranibizumab than with dexamethasone (12.86 vs 2.96 letters; difference 9.91 letters, 95% confidence interval [6.51-13.30]; P.0001). Mean injection number of ranibizumab was 4.52. Ocular AEs were reported in more patients in the dexamethasone than in the ranibizumab group (86.6% vs 55.6%).Using the European labels, similar efficacy was observed for ranibizumab and dexamethasone at months 1 and 2. However, ranibizumab maintained its efficacy throughout the study, whereas dexamethasone declined from month 3 onward. The main limitation of the study was that dexamethasone patients received only a single treatment during the 6-month study. In clinical practice, dexamethasone retreatment may be required earlier than 6 months. Safety findings were similar to those previously reported.

Background It is unclear whether or not an additional encircling band improves outcome in vitrectomy for pseudophakic retinal detachment (PRD). Also unclear is whether small gauge transconjunctival trocar-guided vitrectomy is as successful as conventional 20 gauge (G) vitrectomy. Methods 257 adult patients with uncomplicated PRD were enrolled in 14 vitreoretinal centres across Germany. Contingent on availability of qualified surgeons, eligible patients were randomly assigned either (i) with ratio 1:1 to 20 G vitrectomy plus encircling band (group E1) or 20 G vitrectomy without any buckle (group C) or (ii) with ratios 1:1:1 to group E1, C or 23/25 G vitrectomy without any buckle (group E2). Treatment success was defined as no indication for any retina reattaching procedure during the follow-up of 6 months. Results Success was reached in 79.0% (=79/100, group E1) versus 73.5% (=72/98, group C) (p=0.558, OR 1.32, 95% CI 0.65 to 2.65. In group E2 87.7% (=50/57) of patients reached success compared with 78.7% (=48/61) in group C, demonstrating non-inferiority of E2 to C regarding the prespecified margin of 0.8 (OR scale; p=0.05, OR 2.17, 95% CI 0.80 to 5.89). Best corrected visual acuity significantly increased after surgery independent of technique, that is, on average −0.7 (from 1.0 to 0.3) logMAR. Patients suffered from a shift in spherical refraction of −1.0 D in group E1 compared with −0.1 D in group C. Similarly, intraoperative complications (15.2% vs 8.8% of patients) and serious adverse events (30.3% vs 22.5% of patients) were more frequent in group E1. Conclusions Vitrectomy with gas is an efficient and safe treatment for uncomplicated PRD. An additional encircling band does not significantly reduce the risk for any second procedure necessary to reattach the retina in 20 G vitrectomy. Small gauge transconjunctival vitrectomy is not inferior to the conventional 20 G technique. Trial registration number DKRS 00003158, Results.

Hintergrund Wahrend die intraoperative optische Koharenztomographie (iOCT) im Bereich der Makulachirurgie oder der lamellierenden Keratoplastiken einen sichtbaren Vorteil bringen kann, ist ihr Einsatz bei der Ablatiochirurgie bisher mit unklarem Nutzen verknupft.

Spectral domain optical coherence tomography (SD-OCT) has become a standard diagnostic tool in the surgical management of vitreomacular interface disorders. The high-resolution cross-sectional information obtained from SD-OCT is a perfect complement to vitreoretinal surgery. It provides detailed intraoperative anatomical views that are not possible with a microscope.To investigate the value of intraoperative real-time OCT with respect to improvement of surgical techniques in the management of vitreomacular disorders.A review of the current literature was conducted and an analysis of own systematically evaluated data was included to provide a comprehensive overview of potential applications for the clinical use of intraoperative real-time OCT in macular surgery.Intraoperative real-time OCT can provide detailed visualization of epiretinal membranes and help to identify whether complete membrane removal has been achieved following surgery. In addition, it can provide qualitative and quantitative information that has previously not been available and assist in surgical decision-making. Intraoperative real-time OCT allows membrane peeling to be performed in selected cases without using retinal dyes, whereas it is not ideal for accurately guiding the surgeon while performing maneuvers.Intraoperative real-time OCT provides high-resolution visualization of the effects of surgical maneuvers on the microarchitecture of the retina and surrounding tissues and will fill a gap in the understanding of the pathophysiology and prognostic factors of vitreomacular disorders; however, with currently available systems, accurate intraoperative real-time guidance of surgical maneuvers is hindered by several limiting factors.

Purpose To investigate 12-month outcomes of conversion to aflibercept in patients with neovascular age-related macular degeneration resistant to ranibizumab. Methods Twenty-two eyes of 19 consecutive patients received 3 monthly aflibercept injections followed by a pro re nata protocol. Spectral-domain optical coherence tomography (OCT) images were obtained before each injection. All 49 cross-sectional OCT B-scans obtained in each examination were investigated and the largest choroidal neovascularization (CNV) size was chosen. The same cross-sectional B-scan sections containing the maximum CNV size were used during the follow-up. Results After 12 months, best-corrected visual acuity increased from 45.68 ± 20.25 to 59.09 ± 17.50 Early Treatment Diabetic Retinopathy Study letters (p2 (p = 0.003), and macular volume improved from 9.64 ± 1.75 to 8.45 ± 0.98 mm3 (pConclusions Visual and anatomic improvement were obtained after conversion to aflibercept.

Background and Objectives To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain-optical coherence tomography (SD-OCT) in patients with treatment-resistant neovascular age-related macular degeneration (AMD) who were switched from ranibizumab to aflibercept. Materials and Methods In this prospective case-series, 33 eyes of 30 patients with treatment-resistant neovascular AMD were included. Treatment-resistant neovascular AMD was defined as choriodal neovascularization secondary to AMD determined by subretinal fluid and/or intraretinal fluid/cysts after more than 6 months of monthly ranibizumab therapy. Enrolled eyes were received intravitreal aflibercept injections at weeks 0, 4, and 8. Maximum area of CNV lesion in the cross-sectional area in the B-scan was measured using Heidelberg Eye Explorer software. The same cross-sectional sections containing maximum area of CNV lesion were used during the follow-up. CNV subtypes were determined based on fluorescein angiography images prior to ranibizumab therapy. Main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and area of CNV lesion. Results There were five classic (15%), seven minimally classic (21%), and 21 occult subtypes of CNV (64%). Four weeks after the third injection, BCVA improvement and reduction of the retinal thickness in nine standard ETDRS subfields were significant (both P

Selective retina therapy (SRT) targets the retinal pigment epithelium (RPE) with pulsed laser irradiation by inducing microbubble formation (MBF) at the intracellular melanin granula, which leads to selective cell disruption. The following wound healing process rejuvenates the chorio-retinal junction. Pulse energy thresholds for selective RPE effects vary intra- and interindividually. We present the evaluation of an algorithm that processes backscattered treatment light to detect MBF as an indicator of RPE cell damage since these RPE lesions are invisible during treatment. Eleven patients with central serous chorioretinopathy and four with diabetic macula edema were treated with a SRT system, which uses a wavelength of 527 nm, a repetition rate of 100 Hz, and a pulse duration of 1.7 μs. Fifteen laser pulses with stepwise increasing pulse energy were applied per treatment spot. Overall, 4626 pulses were used for algorithm parameter optimization and testing. Sensitivity and specificity were the metrics maximized through an automatic optimization process. Data were verified by fluorescein angiography. A sensitivity of 1 and a specificity of 0.93 were achieved. The method introduced in this paper can be used for guidance or automatization of microbubble-related treatments like SRT or selective laser trabeculoplasty.

The study analyses patients' risk factors to determine prognostic and predictive factors in patients with acute central retinal artery occlusion (CRAO) treated in the randomized European Assessment Group for Lysis in the Eye (EAGLE) Study with local intra-arterial fibrinolysis (LIF) or conservative standard treatment (CST). These data could improve patient selection for either method.Post hoc statistical analysis of effects of risk factors on overall best corrected visual acuity (BCVA [logarithm of the minimum angle of resolution (logMAR)]) at baseline and month 1 (prognostic effect) and on the difference between outcome of CST and LIF (predictive effect) was conducted.Seventy two of 84 EAGLE datasets were included. Prognostic effect: Patients with coronary heart disease (CHD) presented worse BCVA at baseline (0.39 logMAR, p = 0.0097). Patients with time from occlusion to treatment12 h showed a trend to better vision gain at month 1 (-0.23 logMAR, p = 0.086), similarly smoking (-0.24 logMAR, p = 0.077). Predictive effect: Age (60 years favours LIF -0.54 logMAR;70 years favours CST 0.28 logMAR; interaction p = 0.070) and CHD (favours CST 0.44 logMAR; interaction p = 0.073) might be predictors of therapeutic outcome. There were no strong effects in multivariate analysis.CHD, time from occlusion to treatment and smoking influence BCVA at baseline and at month 1 (prognostic effect). Patients treated within 12 h are more likely to profit from treatment. In multivariate analysis, there is no clear trend to benefit from LIF even in patients with young age, no CHD and early treatment. Based on this preliminary report on a rather small sample size, we do not recommend LIF in CRAO patients.

Purpose To analyze the underlying risk factors in patients with nonarteritic central retinal artery occlusion (CRAO) in a well-defined and homogenous group of patients enrolled in the European Assessment Group for Lysis in the Eye (EAGLE) study. Design Analysis of the cardiovascular risk factors in a prospective, randomized clinical trial. Participants Seventy-seven EAGLE patients with nonarteritic CRAO. Methods Analysis of vascular risk factors and underlying diseases detected by questionnaire and standardized physical examination within 1 month after occlusion. Main Outcome Measures The standardized physical examination included carotid Doppler ultrasonography, echocardiography, electrocardiography, blood pressure monitoring, pulse rate, urine analysis, body mass index analysis, and laboratory tests. Results Seventy-seven of 84 patients had complete datasets for analysis. Fifty-two (67%) patients had cardiovascular risk factors in their medical history, and comprehensive phenotyping identified at least 1 new risk factor in 60 patients (78%; 95% confidence interval, 67%–87%). Thirty-one (40%) had carotid artery stenosis of at least 70%. Eleven patients experienced a stroke, 5 of those within 4 weeks after the CRAO occurred. Arterial hypertension was found in 56 (73%) patients and was newly diagnosed in 12 (16%) study participants. Cardiac diseases were also highly prevalent (22% coronary artery disease, 20% atrial fibrillation, and 17% valvular heart disease). Conclusions Previously undiagnosed vascular risk factors were found in 78% of all CRAO patients. The most meaningful risk factor was ipsilateral carotid artery stenosis. A comprehensive and prompt diagnostic work-up is mandatory for all CRAO patients.

Treatment of retinal vein occlusion can be systemic or local. Therapeutic strategies include improved blood supply, treatment of the vision-reducing macular edema by intravitreal injection of inhibitors of vascular endothelial growth factors (VEGF) or corticosteroids and laser photocoagulation for neovascular complications. As long as head-to-head studies comparing steroids and VEGF inhibitors have not been published, none of the available intravitreally injected substances can be given priority. Well-known side effects of intravitreal steroids are cataract formation and ocular hypertension whereas VEGF inhibitors need to be frequently injected. Although therapy for retinal vein occlusion is protracted, initial long-term data indicate that treatment can be terminated in at least half of the patients . Finally, a treatment recommendation according to the current state of data is presented.

Bernd Junker,1 Jens F Jordan,2 Carsten Framme,1 Amelie Pielen1 1University Eye Hospital, Medical School Hannover, Hannover, 2Eye Center, Medical Center, University of Freiburg, Freiburg, Germany Importance: This study is the first description of the use of the intraoperative optical coherence tomography (iOCT) for trabecular meshwork surgery with the Trabectome in a regular clinical setting.Background: The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork.Design: This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover.Participants: A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study.Methods: All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA) before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients) or without lens (view from above, five patients).Main outcome measures: The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork.Results: Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients.Conclusion: The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT. Keywords: glaucoma, imaging, iOCT, trabecular meshwork surgery

Amelie Pielen,1,2 W Lloyd Clark,3 David S Boyer,4 Yuichiro Ogura,5 Frank G Holz,6 Jean-Francois Korobelnik,7,8 Brigitte Stemper,9,10 Friedrich Asmus,9 Kay D Rittenhouse,11 Christiane Ahlers,9 Robert Vitti,12 Namrata Saroj,12 Oliver Zeitz,9,13,14 Julia A Haller15 On behalf of the COPERNICUS and GALILEO study group 1Eye Center, University Hospital Freiburg, Eye Hospital, Freiburg, 2Hannover Medical School, University Eye Hospital, Hannover, Germany; 3Palmetto Retina Center, Columbia, SC, USA; 4Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA; 5Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 6Department of Ophthalmology, University of Bonn, Bonn, Germany; 7Service d’ophtalmologie, CHU de Bordeaux, 8Service d’ophtalmologie, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team LEHA, UMR 1219, Bordeaux, France; 9Bayer AG, Berlin, 10Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany; 11Bayer US LLC, Whippany, NJ, 12Regeneron Pharmaceuticals, Tarrytown, NY, USA; 13AKH Eye Clinic, Braunschweig, 14Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde, Hamburg, Germany; 15Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA Objectives: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. Patients and methods: Patients were randomized to receive intravitreal aflibercept 2mg every 4weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. Results: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in&nbsp

PURPOSE Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT-A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients. METHODS Thirty patients with primary open-angle glaucoma (mean age: 72.6 ± 7.1 years) and 21 healthy patients (mean age: 70.3 ± 8.6 years) were recruited. Patients received perimetry and OCT measurements of the peripapillary retinal nerve fibre layer thickness (RNFLT) and macular retinal thickness and OCT-A of the macular area in the superficial and deep retinal (DR) plexus. Flow density of the OCT-A scan was calculated by binarisation and quantification of the pixel density. RESULTS Macular flow density was globally and nasally reduced in glaucoma patients in the superficial (globally: p = 0.0203; nasally: p = 0.0003) and DR plexus (globally: p = 0.0113, nasally: p

Purpose The COMRADE studies are the first randomized controlled head-to-head trials comparing the efficacy and safety of intravitreal ranibizumab versus dexamethasone (DEX) in patients with macular oedema secondary to retinal vein occlusion (RVO). The COMRADE extension trial was designed to provide additional 6-month data of patients who completed the core studies. Methods In this open-label, phase IV study patients who completed the COMRADE core studies were prospectively enrolled. Overall, 92 branch RVO (BRVO) patients (ranibizumab 52, DEX 40) and 83 central RVO (CRVO) patients (ranibizumab 61, DEX 22) were treated, and 94.6% of BRVO patients and 97.6% of CRVO patients completed the extension study. Patients were assigned to the same treatment group as in the core studies. Patients were monitored monthly and received either 0.5 mg ranibizumab or a 0.7 mg DEX implant as needed. Results Over the course of the extension, treatment-emergent adverse events (TEAEs) of the study eye occurred in 55.8% of BRVO patients on ranibizumab and in 62.5% of those on DEX. Among CRVO patients, 65.5% in the ranibizumab group and 59.1% in the DEX group developed TEAEs. Overall, elevated intraocular pressure (IOP) was more frequent with DEX than ranibizumab treatment. Mean average change in best-corrected visual acuity (BCVA) in BRVO patients was significantly better for ranibizumab than DEX (p = 0.0249). The CRVO results were consistent with BRVO's, although not significant (p = 0.1119). Conclusion When used according to the European labels, ranibizumab revealed a better ocular safety profile and produced greater average BCVA gains than DEX. By the end of the additional 6-month study period, this difference in BCVA was more pronounced in BRVO as in CRVO patients. The main limitation of the COMRADE studies was that DEX patients received only a single intravitreal treatment during the first 6 months, which is presumably not adequate. However, frequent DEX implants could lead to more steroid-related side effects, especially to an increased intraocular pressure.

Purpose: This is a prospective, randomized, multicenter, investigator-initiated trial to evaluate the 12-month effectiveness of isovolemic hemodilution (IH) with prompt versus deferred intravitreal injections (IVI) of ranibizumab 0.5 mg for the treatment of macular edema secondary to early central retinal vein occlusion (CRVO). Methods: Eyes with macular edema due to CRVO having occurred not more than 8 weeks previously received either monthly ranibizumab IVI in combination with IH (group I, n = 28) or IH alone (group II, n = 30). From month 2 to 12, the patients in both groups could be treated with monthly intravitreal ranibizumab. The main outcome variables were gain of visual acuity and the course of central retinal thickness as measured with optical coherence tomography. Results: At 12 months, eyes in group I on average gained +28.1 (±19.3) letters compared to +25.2 (±20.9) letters in group II (p = 0.326). This result was achieved with significantly fewer injections in group II. Additionally, 30% of the eyes in group II did not need ranibizumab IVI during the 12 months of the trial. Conclusion: Ranibizumab IVI in addition to IH proved to be highly effective in increasing visual acuity and reducing macular edema secondary to CRVO. Initial IH in early CRVO may be a first treatment option in patients anxious about IVI.

Purpose To compare standard-of-care grid laser photocoagulation versus intravitreal ranibizumab (IVR) versus a combination of both in the treatment of chronic (>3 months) macular oedema secondary to branch retinal vein occlusion. Methods Prospective, randomized, multicentre clinical trial. Thirty patients with a best-corrected visual acuity (BCVA) between 20/320 and 20/40 were randomized 1:1:1 to receive grid laser or three monthly injections of 0.5 mg IVR or both followed by 3 months of observation. Results Mean change from baseline BCVA at month 6 was +2 letters [laser; 0.04 logMAR, 95% confidence interval (−0.17; 0.25)], +17 letters [IVR; 0.34 (0.19; 0.5)] and +6 letters [combination; 0.12 (0.01; 0.24)] (IVR versus laser p = 0.02 and IVR versus combination p = 0.02). At month 3, mean improvement in central retinal thickness (CRT) was 90.6 μm (laser) (−18.65; 199.8), 379.5 μm (IVR) (204.2; −554.8), and 248 μm (167.2; −328.8) (combination) (IVR versus laser p = 0.005, laser versus combination p = 0.02). During the observation period, CRT improved in laser [37.6 μm (−66.82; 142.0)], but deteriorated in IVR [−142.4 μm (−247.6; −37.16)] and combination [−171.7 μm (−250.4; −92.96)] (laser versus IVR p = 0.01, laser versus combination p = 0.002) indicating recurrent oedema. Less laser retreatments (at 8 weeks) were required in combination group (2/10) than grid group (7/10). Conclusion Six-month results suggest that ranibizumab may be superior to grid laser in improving visual acuity. Grid combined with IVR neither enhanced functional and morphological improvement of IVR nor did it prevent or prolong recurrence of oedema. In IVR groups, CRT increased slowly after stopping injections, whereas improvement in visual acuity was sustained, indicating that morphological changes occur prior to functional impairment.

Purpose To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. Methods This was a retrospective comparative analysis of 20-G and 23-G vitrectomy (introduced in 2007) for macular surgery due to macular pucker or macular hole performed between 2006 and 2010 in 61 and 59 eyes, respectively, by 2 experienced surgeons and 2 trainees. We assessed the adjusted hazard ratio for vitrectomy 23-G vs 20-G with a Cox proportional hazard model. We counted retinal detachment, vitreous hemorrhage, endophthalmitis (as early postoperative complications), or cataract progression (as late postoperative complication) as endpoint. We adjusted for indication, surgeon, retinopexy method, and the endotamponade. Results Follow-up averaged 712 days. Median time to first event was 385 days in the 23-G group and 342 days in the 20-G group. Cox proportional hazard analysis showed no significant difference between vitrectomy 23-G vs 20-G with regard to postoperative complications (hazard ratio 0.79, 95% confidence interval 0.41-1.52). The other covariates did not exert a statistically significant effect on the risk of adverse events. Looking at individual complications, retinal detachment was exclusively found after 20-G. Conclusions In this homogenous large cohort, we did not find a statistically significant difference in rates of complications between 23-G and 20-G vitrectomy techniques for macular surgery. Trainees performed equally well as experienced surgeons.

Cysteine cathepsins are a family of proteases involved in intracellular protein turnover and extracellular matrix degradation. Cathepsin B (Ctsb) and cathepsin Z (Ctsz) promote tumorigenesis and Ctsb is a known modulator of tumor angiogenesis. We therefore investigated the angiomodulatory function of these cathepsins in vitro as well as in a mouse model of laser-induced choroidal neovascularization (laser-CNV). Ctsb−/−, Ctsz−/−, Ctsb/Ctsz double-knockout (Ctsb/z DKO), and wild type (WT) mice underwent argon laser treatment to induce choroidal neovascularization (CNV). The neovascularized area was quantified individually for each lesion at 14 days after laser coagulation. In vitro the effects of cathepsin inhibitors on angiogenesis were analysed by endothelial cell (EC) spheroid sprouting and EC invadosome assays. Retinas from cathepsin KO mice did not show gross morphological abnormalities. In the laser CNV model, however, Ctsb/z DKO mice displayed a significantly reduced neovascularized area compared to WT (0.027 mm2 vs. 0.052 mm2; p = 0.012), while single knockouts did not differ significantly from WT. In line, VEGF-induced EC spheroid sprouting and invadosome formation were not significantly altered by a specific cathepsin B inhibitor alone, but significantly suppressed when more than one cathepsin was inhibited. Our results demonstrate that laser-CNV formation is significantly reduced in Ctsb/z DKO mice. In line, EC sprouting and invadosome formation are blunted when more than one cathepsin is inhibited in vitro. These results reveal an angiomodulatory potential of cathepsins with partial functional redundancies between different cathepsin family members.

Fingolimod 0.5-mg once-daily is an approved therapy for patients with relapsing–remitting multiple sclerosis (MS). Several pivotal and real-world studies have demonstrated that fingolimod is associated with the development of macular edema (ME). Herein, we present a case of a diabetic MS patient who developed severe bilateral ME during fingolimod treatment. By means of this case study we provide a detailed review about fingolimod associated macular edema (FAME), its current incidence with or without diabetes mellitus, and previous therapy attempts and outcomes in MS patients. Intravitreal administration of antibodies raised against vascular endothelial growth factor A (VEGF-A) has not yet been used in the management of FAME, however, the excellent therapeutic response in our patient may justify the use of anti-VEGF-A agents in combination with cessation of fingolimod to achieve fast resolution of FAME and to prevent visual deficits, particularly in bilateral FAME. OA gold

Purpose: To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Methods: Patients received eithermonthly ranibizumabfor 3 months followed byPro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followedbyPRNshaminjections (n = 118).Mainoutcomesweremeanaveragechange in best-corrected visual acuity(BCVA)frombaseline tomonth1throughmonth6,mean changes inBCVAand foveal centre point thickness (FCPT), and adverse events (AEs). Results: There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 ( 11) letters versus+9.3 ( 10.1) letters].Atmonth 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Conclusion: Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point.

To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain-optical coherence tomography (SD-OCT) in patients with treatment-resistant neovascular age-related macular degeneration (AMD) who were switched from ranibizumab to aflibercept.In this prospective case-series, 33 eyes of 30 patients with treatment-resistant neovascular AMD were included. Treatment-resistant neovascular AMD was defined as choriodal neovascularization secondary to AMD determined by subretinal fluid and/or intraretinal fluid/cysts after more than 6 months of monthly ranibizumab therapy. Enrolled eyes were received intravitreal aflibercept injections at weeks 0, 4, and 8. Maximum area of CNV lesion in the cross-sectional area in the B-scan was measured using Heidelberg Eye Explorer software. The same cross-sectional sections containing maximum area of CNV lesion were used during the follow-up. CNV subtypes were determined based on fluorescein angiography images prior to ranibizumab therapy. Main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and area of CNV lesion.There were five classic (15%), seven minimally classic (21%), and 21 occult subtypes of CNV (64%). Four weeks after the third injection, BCVA improvement and reduction of the retinal thickness in nine standard ETDRS subfields were significant (both P 0.001). Regarding and regardless of CNV subtypes, mean area of CNV lesion decreased significantly at final visit. Overall, a dry macula was achieved in 21 eyes (64%) and 12 eyes (36%) showed decreased or unchanged edema.Switching to aflibercept seems to result in reduction of CNV lesion area in short-term follow-up of patients with treatment-resistant neovascular AMD. Lasers Surg. Med. 48:668-677, 2016. © 2016 Wiley Periodicals, Inc.

Der Begriff des okularen Ischamiesyndrom (OIS) bezeichnet verschiedene krankhafte Augenveranderungen, die durch eine chronische arterielle Verschlusserkrankung, in der Regel der A. carotis interna, verursacht werden. Fuhrende okulare Symptome sind Visusverschlechterung und Schmerzen. Die Erkrankung ist selten und kann leicht mit einer diabetischen Retinopathie oder einem alteren Zentralvenenverschluss verwechselt werden. Die augenarztliche Therapie beschrankt sich auf die Behandlung der neovaskularen Komplikationen. Besondere Bedeutung hat die interdisziplinare internistische und neurologische Abklarung, da die zugrunde liegenden Begleiterkrankungen mit einer deutlich erhohten Mortalitat einhergehen. In diesem Beitrag werden die klinischen Formen des OIS sowie die diagnostischen und therapeutischen Moglichkeiten diskutiert.

Central retinal artery occlusion (CRAO) is an ophthalmological emergency situation. Known risk factors are arterial hypertension, cardial arrhythmia, arteriosclerosis, hypercholesterolemia and diabetes. Elderly patients should be examined for an arteritic genesis. Young patients (< 45 years) without typical risk factors may suffer from thrombophilia. There is no uniform recommendation on how to treat non-arteritic CRAO. Many different interventions have been suggested in the literature, i. e., massaging the eye, systemic or local reduction of intraocular pressure, anticoagulation, either systemically administered venous thrombolysis or supraselective intra-arterial thrombolysis. In this review we present the causes of CRAO and diagnostic means to detect causes; we also critically discuss previously described therapeutic options. It is our aim to provide a guide through the necessary interdisciplinary diagnostics in co-operation with internal medicine and neurology and to recommend a multimodal therapy in patients with non-arteritic CRAO.

The novel therapeutic principle of intravitreal drug therapy for retinal vein occlusion has become an integrated constituent of clinical practice over the last years. The two substance classes that have been evaluated in large randomised clinical trials so far are corticosteroids and inhibitors of vascular endothelial growth factor (VEGF). The reported treatment success of these intravitreally administered substances has lead not only to a paradigm shift in clinical care but has also advanced our understanding of the underlying pathophysiological principles of retinal vein occlusions. In this review the different substances are discussed, their mechanisms of action are analysed and the results of the large clinical trials available to date are critically evaluated. Furthermore, an approach to integrate these novel treatment options into the exisitng treatment regimes for retinal vein occlusions is suggested.

Background To identify predictive factors for improvement of visual acuity and central retinal thickness by intravitreal bevacizumab for the treatment of macular edema (ME) due to branch retinal vein occlusion (BRVO). Methods Two hundred and five eyes from 204 patients with ME secondary to BRVO were retrospectively included at six sites. All eyes received intravitreal bevacizumab therapy (1.25 mg/0.05 ml). The mean follow-up was 36.8 ± 12.7 weeks (range, 18 to 54 weeks). Measurement of ETDRS best-corrected visual acuity (BCVA, in all eyes) and optical coherence tomography (OCT, in 87% of eyes) were performed at baseline and at follow-up examinations every 12 weeks. Using fluorescein angiography, the perfusion status of the macula at baseline could be assessed in 84% of the eyes. The main outcome measures were changes in BCVA and central retinal thickness (CRT). For analysis of predictive factors, the results at 24 weeks were used. Results The median BCVA was 0.6 LogMAR at baseline and improved to 0.4 LogMAR at 24 and 48 weeks. This visual improvement was associated by a significant reduction in CRT, decreasing from a baseline of 454 μm to 267 μm and 248 μm after 24 and 48 weeks respectively. Eyes with ME and intact (perfused) or interrupted (ischemic) foveal capillary ring showed a 2-line increase of median BCVA [45 eyes (22%) and 128 eyes (62%) respectively]. However, the final median BCVA was significantly worse in eyes with ischemic ME (0.6 versus 0.3 logMAR in perfused ME). Other factors for visual improvement were absence of previous treatments of the ME, age younger than 60 years and low baseline BCVA (≥0.6 logMAR) (2, 3, and 2 median BCVA lines increase respectively). Furthermore, eyes with duration of the ME of less than 12 months responded with a 3-line increase of the median BCVA. Final CRT only showed minor differences between the subgroups. During the entire follow-up, retreatments were performed in 85% of the eyes, with a median number of injections of three (mean 3.2; range, 1 to 10) and a median time-interval between injections of 11.6 weeks (mean 14.6 weeks). Conclusions Intravitreal injection of bevacizumab resulted in a significant improvement of BCVA and reduction of ME in BRVO. Baseline BCVA, patient’s age, and duration of BRVO were found to be of prognostic relevance for visual improvement. A less favorable outcome of the bevacizumab therapy in eyes with longstanding BRVO would advocate initiation of treatment within 12 months after onset.