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To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Zusammenfassung Hintergrund Die Beurteilung der intraoperativen Veränderung der Netzhautmorphologie, insbesondere des vitreoretinalen Überganges, ist mithilfe der intraoperativen optischen Kohärenztomografie (iOCT) möglich geworden. Ziel der Arbeit Um die Bedeutung der intraoperativen Morphologie beim durchgreifenden Makulaforamen (MF) für das postoperative funktionelle Ergebnis zu evaluieren, wurde eine retrospektive, klinische Beobachtungsstudie durchgeführt. Material und Methoden Die Netzhautmorphologie wurde in 32 Augen von 32 konsekutiven Patienten mit durchgreifendem Makulaforamen mittels iOCT zu verschiedenen Zeitpunkten während der Operation beobachtet. Die Veränderungen wurden anschließend mit dem postoperativen funktionellen Ergebnis korreliert. Ergebnisse Nach Induktion der hinteren Glaskörperabhebung (HGA) reduzierte sich der Makulaforamen-Index (MHI) um −0,05 (p = 0,01), die basale Foramenbreite (FB) stieg um +99,4 μm (SD = 197,8 μm; p = 0,04). Die Verschlussrate betrug 100 % zum Zeitpunkt der ersten postoperativen Vorstellung nach im Mittel 73 Tagen, der postoperative Visus verbesserte sich signifikant (p Es zeigte sich eine signifikant positive Korrelation von intraoperativer Morphologie und postoperativem Ergebnis zwischen einem niedrigen MHI und einem besseren postoperativen Visus (SKK = 0,50; p = 0,02), zwischen einer großen FB und einem besseren postoperativen Visus (SKK = 0,43; p = 0,05) sowie zwischen einer breiten Apertur nach HGA und einem größeren Visusanstieg postoperativ (SKK = 0,44; p = 0,03). Diskussion Wir konnten eine Abflachung sowie eine Verbreiterung des MF durch Lösen der vitreoretinalen Zugkräfte beobachten. Aufgrund des Zusammenhangs zwischen einer großen intraoperativen FB mit einem besseren postoperativen Visus scheint die intraoperative Relaxierung der Netzhaut bedeutsam.

PURPOSE To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane. METHODS Patients were included who had successful surgery for macular hole

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1–G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, ppp=0.072) and 52.4% of eyes with G5 (ppp

Purpose To investigate morphological and functional outcomes of the inverted internal limiting membrane (I-ILM) flap technique in large (≥ 400 μm) idiopathic full-thickness macular holes (FTMH) over a follow-up period of 12 months. Methods In this retrospective study, 55 eyes of 54 consecutive patients were enrolled. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT, Heidelberg, Spectralis) were performed preoperatively as well as 1, 3, 6, 9, and 12 months postoperatively. Special focus was put on the reintegration of outer retinal layers and the different ILM flap appearances. Results FTMH closure rate was 100% (55/55). BCVA significantly improved over the follow-up period of 12 months from 0.98 ± 0.38 LogMAR preoperatively to 0.42 ± 0.33 LogMAR at 12 months postoperatively (p Conclusion Our study highlights the favorable morphological and functional outcomes of the I-ILM flap technique in the short as well as in the long term. While complete ELM restoration revealed to be an important factor for improvement in BCVA, the different postoperative ILM flap appearances seem not to be related to BCVA.

Subretinal injection is a delicate and complex microsurgery. The main surgical difficulties come from the surgeon's hand tremor, dexterous motion, and insufficient visual feedback. In order to begin addressing these challenges, this article presents a robot system for subretinal insertion integrated with intraoperative optical coherence tomography (OCT). The surgical workflow using this system consists of two main parts. The first part is the manual robot control, which aims the target before approaching the retinal surface, while considering the remote center of motion (RCM) constraint. When the injection area has been located precisely, needle is inserted into retina. To ensure surgical safety, needle insertion depth is estimated using OCT images on a continuous basis. A soft RCM control method is designed and integrated for the controller of our hybrid parallel–serial surgical robot. Safety and accuracy performance evaluation with a 15-ms control loop shows that the worst-case RCM deviation error is within 1 mm. Experimental results demonstrated that the proposed system has the ability to improve surgical outcomes by surgeons overcoming their physical limitations in order to enable a better dexterous motion, and furthermore enhancing their visual feedback for a better intraocular perception.

The treatment options for patients with metastatic melanoma (MM) have been dramatically expanded in recent years with the approval of new drugs. The MEK (mitogen-acitvated protein kinase kinase) and BRAF (serine/threonine-protein kinase B-Raf coding gene) inhibitor combination therapy is currently part of the standard of care for stage IIIC/IV of BRAF mutant melanoma. The MEK inhibitor-associated retinopathy (MEKAR) is observed in patients with MM who are treated (or have been treated) with such a combination therapy. This article reports the case of a 72-year-old male patient, who suffered from such a pathological condition under treatment with binimetinib in combination with nivolumab. This case study illustrates the importance of interdisciplinary collaboration in the treatment of MM patients.Die Behandlungsmöglichkeiten für Patienten mit metastasierendem Melanom (MM) wurden in den letzten Jahren mit der Zulassung von neuen Medikamenten dramatisch erweitert. Die MEK(mitogen-aktivierte Proteinkinase-Kinasen)- und BRAF(Serin/Threonin-Kinase B-Raf kodierendes Gen)-Hemmer-Kombinationstherapie gehört aktuell zum Versorgungsstandard für das Stadium IIIC/IV des BRAF-mutierten Melanoms. MEKAR (MEK-Inhibitor-assoziierte Retinopathie) werden bei Patienten mit metastasierendem Melanom beobachtet, die mit einer solchen Kombinationstherapie behandelt werden bzw. wurden. Wir berichten über den Fall eines 72-jährigen Patienten, der eine solche Pathologie unter der Therapie mit Binimetinib in Kombination mit Nivolumab erlitt. Diese Kasuistik verdeutlicht die Wichtigkeit einer interdisziplinären Zusammenarbeit bei der Behandlung von MM-Patienten.

The purpose of this study was to assess the repeatability and reproducibility of measuring the minimum linear diameter (MLD) of macular holes (MHs) using horizontal linear and radial scan modes in optical coherence tomography (OCT). Patients with concurrent sets of radial and horizontal linear OCT volume scans were included. The MLD was measured twice in both scan modes by six raters of three different experience levels (groups). Outcome measures were the reliability and repeatability of MLD measurements. Fifty patients were included. Mean MLD was 317.21(±170.63) µm in horizontal linear and 364.52 (±161.71) µm in radial mode, a difference of 47.31 (±26.48) µm (p &lt, 0.001). In the radial scan mode, MLD was identified within 15° of the horizontal meridian in 27% and within 15° of the vertical meridian in 26.7%, with the remainder (46.3%) in oblique meridians. The intra-group coefficients of repeatability (CR) for horizontal linear mode were 23 µm, 33 µm and 45 µm, and for radial mode 25 µm, 44 µm and 57 µm for groups 1, 2 and 3, respectively. The inter-group CR, taking group 1 as reference standard for groups 2 and 3, were 74 µm and 71 µm for the linear mode, and 62 µm and 78 µm for radial mode. The radial mode provides good repeatability and reliability for measurement of MLD. In a majority of cases the MLD does not lie in the horizontal meridian and would be underestimated using a horizontal OCT mode.

Purpose The purpose of this study was to develop methods to model the external limiting membrane (ELM) and ellipsoid zone (EZ) within the elevated cuff surrounding a macular hole (MH) to determine if the predicted size of the defect in these layers after virtual flattening was associated with the actual postoperative defect and best-corrected visual acuity (BCVA). Methods Patients were included who had undergone successful MH surgery. The defects in the ELM and EZ after virtual flattening were modeled using in-house software. Main outcomes were postoperative defects in ELM and EZ at 2 months and BCVA at 12 months. Results Fifty-eight patients were included. BCVA improved from 0.87 (0.31) logMAR pre-operatively to 0.26 (0.21) at 12 months (P < 0.001). For both the ELM and EZ, the predicted virtually flattened pre-operative defects were associated with the actual postoperative defects at 2 months (R2 = 0.33, P < 0.01 and R2 = 0.50, P < 0.01, respectively). There was a significant association of BCVA at 12 months (adjusted R2 = 0.85) with the pre-operative modeled area of the defect in the ELM (P < 0.01) and to a lesser extent with the defect in the EZ (P < 0.01) and base of the MH (P < 0.01). Conclusions Virtually flattening of the pre-operative defect in the ELM provides important predictive information of visual acuity. Incorporation of tools into commercially available optical coherence tomography (OCT) devices to facilitate such measurements would provide the clinician with important prognostic information. Translational Relevance We have developed methodology that can potentially be used to predict the postoperative state of the outer retinal layers and the associated visual outcome in patients undergoing surgery for MH.

To assess the effect of an internal limiting membrane flap (IF) in macular hole surgery on the best-corrected visual acuity (BCVA) and integrity of the ellipsoid zone (EZ) and external limiting membrane.Patients were included who had successful surgery for macular hole400 µm with or without an IF. Main outcome measures were BCVA and restoration of the external limiting membrane and EZ at 12 months.Sixty patients were included, 36 with conventional peeling and 24 with an IF. The best-corrected visual acuity improved from 0.74 (±0.30) logarithm of the minimum angle of resolution (20/110 Snellen) to 0.26 (±0.20) (20/36 Snellen) in patients without and from 0.77 (±0.32) logarithm of the minimum angle of resolution (20/118 Snellen) to 0.18 (±0.12) (20/30 Snellen) in patients with an IF, respectively. There was no difference in the integrity of the EZ and external limiting membrane in patients with or without an IF at either 3 (P = 0.58, P = 0.20), 6 (P = 0.81, P = 0.10), or 12 months (P = 0.60, P = 0.20) or in the BCVA at 3 (P = 0.24), 6 (P = 0.18) and 12 months (P = 0.11). In the multivariable model, only preoperative BCVA (P0.01), EZ integrity (P = 0.001), and age (P0.01) were associated with the post-operative BCVA.In patients undergoing surgery for macular hole400 µm, the use of an IF did not affect the BCVA or the integrity of the EZ and external limiting membrane.

Purpose To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. Methods In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. Results SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. Conclusion SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

Machine learning and especially deep learning techniques are dominating medical image and data analysis. This article reviews machine learning approaches proposed for diagnosing ophthalmic diseases during the last four years. Three diseases are addressed in this survey, namely diabetic retinopathy, age-related macular degeneration, and glaucoma. The review covers over 60 publications and 25 public datasets and challenges related to the detection, grading, and lesion segmentation of the three considered diseases. Each section provides a summary of the public datasets and challenges related to each pathology and the current methods that have been applied to the problem. Furthermore, the recent machine learning approaches used for retinal vessels segmentation, and methods of retinal layers and fluid segmentation are reviewed. Two main imaging modalities are considered in this survey, namely color fundus imaging, and optical coherence tomography. Machine learning approaches that use eye measurements and visual field data for glaucoma detection are also included in the survey. Finally, the authors provide their views, expectations and the limitations of the future of these techniques in the clinical practice.

Ophthalmic microsurgery is known to be a challenging operation, which requires very precise and dexterous manipulation. Image guided robot-assisted surgery (RAS) is a promising solution that brings significant improvements in outcomes and reduces the physical limitations of human surgeons. However, this technology must be further developed before it can be routinely used in clinics. One of the problems is the lack of proper calibration between the robotic manipulator and appropriate imaging device. In this work, we developed a flexible framework for hand-eye calibration of an ophthalmic robot with a microscope-integrated Optical Coherence Tomography (MIOCT) without any markers. The proposed method consists of three main steps: a) we estimate the OCT calibration parameters; b) with micro-scale displacements controlled by the robot, we detect and segment the needle tip in 3D-OCT volume; c) we find the transformation between the coordinate system of the OCT camera and the coordinate system of the robot. We verified the capability of our framework in ex-vivo pig eye experiments and compared the results with a reference method (marker-based). In all experiments, our method showed a small difference from the marker based method, with a mean calibration error of 9.2 $\mu$m and 7.0 $\mu$m, respectively. Additionally, the noise test shows the robustness of the proposed method., Comment: *The first two authors contributed equally to this paper. Accepted by IEEE Robotics and Automation Letters (RA-L), 2018

To investigate safety of accelerated corneal crosslinking during the first postoperative month. In this retrospective study, 76 eyes of 60 patients with verified progressive keratectasia were enrolled in this study and followed for 1 month after accelerated CXL (18 mW/cm2 for 5 min, radiant exposure 5.4 J/cm2) (A-CXL(5*18)). Preoperatively, objective refraction, slit lamp inspection, and corneal tomography were performed. Early postoperative slit lamp examinations were performed on days 1 and 4. At 1 month, objective refraction, slit lamp inspection, and corneal tomography were performed. Gender distribution was m:f = 55:21, OD:OS was 40:36, and the average age was 26.5 ± 8.6 years at surgery. Only 71 of the 76 eyes completed the 1-month follow-up, indicating a dropout rate of 6.6%. In 7.0% (n = 5), sterile infiltrates were observed; 5.6% of eyes (n = 4) showed delayed epithelial healing (> 4 days) in 2.8% (n = 2); an infection occurred and in 1 eye (1.4%), a stromal scar was detected; no other complications, neither a loss of two or more Snellen lines at 1 month postoperatively, were observed. As a risk factor for sterile infiltrates, thin preoperative pachymetry could be identified (p = 0.027). This study revealed no difference in early postoperative safety between CXL using 18 mW/cm2 and standard corneal CXL. Thinner preoperative pachymetry could be identified predicting a higher rate of postoperative sterile infiltrates.

PurposeThe purpose of this study was to determine a cutoff for progression of idiopathic full-thickness macular hole (MH) size.MethodsRetrospective analysis of consecutive patients waiting 4 weeks for MH surgery. Two observers performed 3 repeat sets of MH size measurements on optical coherence tomography (OCT) high-density radial scans taken at first presentation and 4 weeks later before surgery. Primary outcome was the definition of a cutoff for true enlargement of MH size versus measurement error. Secondary outcomes were risk factors for change in minimum linear diameter (MLD) size and best-corrected visual acuity (BCVA).ResultsFifty-one patients were included with a mean MH size of 334 µm (±179 µm; range 39 to 793 µm). The cutoff for an increase in MLD size calculated as the outer confidence limit for the 99.73% limits of agreement was 31 µm. This was independent of MH size. Using this cutoff, MLD size increased in 9/34 (26.5%) of patients without and in 14 of 17 (82.4%) of patients with vitreomacular traction (VMT; P < 0.001). Mean BCVA deteriorated in patients in whom the MH had progressed from 0.62 (±0.23) logMAR to 0.82 (±0.29; P < 0.001), whereas there was no significant change in BCVA in patients without MH progression (P = 0.25). In 31% (16/51) of patients, classification of their MHs (small ≤250 µm, medium 251-400 µm, and large >400 µm) changed over the 4-week period.ConclusionsUsing a cutoff discriminates change from measurement error. A significant proportion of MHs progressed by 4 weeks, particularly in the presence of VMT.Translational relevanceThe established cutoff enables clinicians to differentiate true MH enlargement from measurement error.

ZusammenfassungArterielle Gefäßverschlüsse sollten als Notfall bewertet werden und sind als okuläres Analogon zum zerebralen Apoplex zu sehen. Sie besitzen dieselben arteriosklerotischen Risikofaktoren, die auch bei Herz-, Kreislauf- und zerebrovaskulären Erkrankungen ursächlich sind, weshalb eine intensive interdisziplinäre Abklärung erforderlich ist, um mögliche Komorbiditäten rechtzeitig zu erkennen und gegebenenfalls zu behandeln. Die derzeitigen Therapiemöglichkeiten eines akuten arteriellen Gefäßverschlusses sind in ihrer Effizienz hinsichtlich Visusverbesserung sehr limitiert. Verfahren zur systemischen Lyse können in der Routineversorgung aufgrund ihres deutlich erhöhten Nebenwirkungsprofils nicht empfohlen werden. Hinzu kommt ein begrenztes Zeitfenster von bis zu 6 Stunden nach Symptombeginn (Retinatoleranzzeit), in dem nach Studienlage eine Intervention überhaupt nur sinnvoll zu sein scheint. Dagegen haben die neuen Therapiemöglichkeiten retinaler Venenverschlüsse, insbesondere durch die intravitreale operative Medikamentenapplikation, zu deutlichen Visusverbesserungen geführt. Die Wirksamkeit und Effizienz der einzelnen Anti-VEGF-Medikamente ist nach aktueller Studienlage vergleichbar. Alternativ kann auch der Einsatz von Steroiden erwogen werden, wobei hierbei das Nebenwirkungsprofil sorgfältig abgewogen werden sollte. Des Weiteren kann ergänzend und gerade beim Vorliegen von retinalen Ischämien die periphere Photolaserkoagulation einen visusstabilisierenden Effekt haben und die Ausbildung von Neovaskularisationen verhindern. Es wird angenommen, dass die Kombination aus IVOM- und Lasertherapie einen symbiotischen Effekt haben könnte.

Zusammenfassung Hintergrund Die hochauflösende optische Kohärenztomografie (OCT) ermöglicht eine kontrastreiche Bildgebung von Mikrostrukturen, die mit konventioneller Bildgebung nicht so detailliert darstellbar waren. Wir berichten über unsere Erfahrungen beim Einsatz der intraoperativen OCT (iOCT) in der vitreoretinalen Chirurgie. Methoden 110 Patienten mit vitreoretinalen Erkrankungen (Makulaforamen, epiretinale Membranen, vitreomakulärem Traktionssyndrom, Ablatio und Glaskörperblutung) wurden unter Visualisierung mit dem im Mikroskop integrierten iOCT-Gerät operiert. Ergebnisse Das iOCT liefert durch die Integration von Mikroskop und SD-OCT eine sofortige Visualisierung der „Region of Interest“ (ROI). Der Operateur erhält neben dem Mikroskopbild die intraoperative Darstellung aller Netzhautschichten, des Glaskörpers sowie der Instrument-Gewebe-Interaktion in Echtzeit und kann diese intraoperativ sofort verfügbare Information für die chirurgische Strategie nutzen. Schlussfolgerung Bisher ist das iOCT nur als Standmikroskop erhältlich, es besitzt keine Messfunktion, keine Tracking-Funktion, und die Metallinstrumente verdecken den Scan. Künftig könnten transparente Instrumente, Tracking-Funktionen, ein Autofokus sowie eine noch bessere Auflösung eine optimierte, lückenlose, hochauflösende intraoperative OCT-Diagnostik in Echtzeit erlauben.

This paper introduces an optimized input device workflow to control an eye surgical robot in a simulated vitreoretinal environment. The input device is a joystick with four Degrees of Freedom (DOF) that controls a six DOFs robot. This aim is achieved through a segmentation plan for an eye surgeon. In this study, the different surgical phases are defined while each phase includes their specific number of DOFs. The segmentation plan is divided into four surgical phases: Phase I: Approach with three DOFs; Phase II: Introduction with three DOFs; Phase III: Aim with 3+1 DOFs; and Phase IV: Injection with one DOF. Taking these phases into consideration, an eye surgical robot with six DOFs could be controlled through a joystick with only four DOFs intuitively. In this work we show that reducing the number of DOFs will decrease the complexity of the surgery with a robotic platform.

Subretinal injection is known to be a complicated task for ophthalmologists to perform, the main sources of difficulties are the fine anatomy of the retina, insufficient visual feedback, and high surgical precision. Image guided robot-assisted surgery is one of the promising solutions that bring significant surgical enhancement in treatment outcome and reduces the physical limitations of human surgeons. In this paper, we demonstrate a robust framework for needle detection and localization in subretinal injection using microscope-integrated Optical Coherence Tomography (MI-OCT) based on deep learning. The proposed method consists of two main steps: a) the preprocessing of OCT volumetric images; b) needle localization in the processed images. The first step is to coarsely localize the needle position based on the needle information above the retinal surface and crop the original image into a small region of interest (ROI). Afterward, the cropped small image is fed into a well trained network for detection and localization of the needle segment. The entire framework is extensively validated in ex-vivo pig eye experiments with robotic subretinal injection. The results show that the proposed method can localize the needle accurately with a confidence of 99.2%.

Background: To assess functional and morphological outcomes in patients with chronic recurrent neovascular age-related macular degeneration (nAMD) previously treated with ranibizumab, who were either switched from ranibizumab to aflibercept or received further ranibizumab injections. Methods: Retrospective analysis of eyes with recurrent nAMD previously treated with ranibizumab. On recurrence of the macular oedema, patients had received either 3 injections of aflibercept (2.0 mg) or ranibizumab (0.5 mg) at 4 week intervals. Patients were examined before the first injection and four weeks after the last injection. The main outcome measures included change in visual acuity (VA) in logMAR, subfoveal central retinal thickness (CRT), subretinal fluid (SRF) and height of pigment epithelial detachment (PED height), as well as the maximum height of macular subretinal fluid (SRF max) and of macular pigment epithelial detachment (PED height max) in spectral-domain optical coherence tomography (OCT). Changes in VA and OCT were compared between the two groups to investigate differences in the therapeutic effects of aflibercept and ranibizumab. Results: 60 eyes of 55 patients were included. The aflibercept group (n = 30) and the ranibizumab group (n = 30) showed no statistically significant differences in mean age (p = 0.813), number of prior injections of ranibizumab (p = 0.127) or time since last injection (p = 0.523). Mean VA logMAR improved in both groups, though only in the ranibizumab group was the difference significant (0.50 ± 0.33 to 0.44 ± 0.29 logMAR; p = 0.013; Table 1). CRT decreased in the aflibercept (p = 0.133) and ranibizumab groups (p = 0.043). PED height was reduced in both groups (aflibercept p = 0.068; ranibizumab p = 0.241). SRF, SRF max and PED height max showed statistically significant decreases in both groups. Comparison of the aflibercept and the ranibizumab groups showed no statistically significant differences between the two groups in change in VA logMAR (p = 0.680), CRT (p = 0.882), SRF (p = 0.871), PED height (p = 0.524), SRF max (p = 0.940) or PED height max (p = 0.762). Conclusions: Aflibercept and ranibizumab were similarly effective in improving visual acuity and morphological parameters of patients with recurrent nAMD after four months. There were no statistically significant differences in the therapeutic effects of the two drugs.

BACKGROUND AND OBJECTIVE: To describe optical coherence tomography angiography (OCTA) findings in patients with acute central serous chorioretinopathy (CSC) compared to conventional imaging methods. PATIENTS AND METHODS: A consecutive series of 11 eyes from 10 healthy patients with acute CSC were included and underwent fluorescein angiography (FA), indocyanine green angiography (ICGA), OCT, fundus autofluorescence (FAF), and OCTA. Obtained OCTA images were evaluated for the presence of serous detachments of the neurosensory retina, leakage points, or other altered findings and compared to conventional imaging devices. RESULTS: In four out of 11 eyes, it was possible to detect detached retina adjacent to the leakage point in OCTA images, compared with four of 11 eyes using FA, five of 11 eyes using ICGA, 11 of 11 eyes using SD-OCT, and four of 11 eyes using FAF. In five out of 11 eyes, irregular flow patterns were observed on OCTA images through the choriocapillaris. OCTA images could not identify leakage points in any of the included eyes, compared with 11 out of 11 eyes on FA, five out of 11 eyes on ICGA, eight out of 11 eyes on SD-OCT, and zero out of 11 eyes on FAF. CONCLUSION: OCTA images of the superficial and deep retinal plexus, outer retina, and choriocapillaris did not reveal altered flow patterns directly associated with the leakage point in acute CSC. However, OCTA was able to visualize altered choroidal flow in some of the included eyes. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:322–327.]

Aim To describe retinal findings of various imaging modalities in acute retinal ischemia. Methods Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), OCT-angiography (OCT-A) and fundus autofluorescence (FAF) images of 13 patients (mean age 64y, range 28-86y) with acute retinal ischemia were evaluated. Six suffered from branch arterial occlusion, 2 had a central retinal artery occlusion, 2 had a combined arteriovenous occlusions, 1 patient had a retrobulbar arterial compression by an orbital haemangioma and 2 patients showed an ocular ischemic syndrome. Results All patients showed increased reflectivity and thickening of the ischemic retinal tissue. In 10 out of 13 patients SD-OCT revealed an additional highly reflective band located within or above the outer plexiform layer. Morphological characteristics were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. OCT-A showed a loss of flow signal in the superficial and deep capillary plexus at the affected areas. Reduced flow signal was detected underneath the regions with retinal edema. FAF showed areas of altered signal intensity at the posterior pole. The regions of decreased FAF signal corresponded to peri-venous regions. Conclusion Multimodal imaging modalities in retinal ischemia yield characteristic findings and valuable diagnostic information. Conventional OCT identifies hyperreflectivity and thickening and a mid-retinal hyperreflective band is frequently observed. OCT-A examination reveals demarcation of the ischemic retinal area on the vascular level. FAF shows decreased fluorescence signal in areas of retinal edema often corresponding to peri-venous regions.

BACKGROUND AND OBJECTIVE: To correlate subfoveal choriocapillaris (CC) flow density with age using spectral-domain optical coherence tomography angiography (SD-OCTA). PATIENTS AND METHODS: One hundred eighty-three eyes of 94 subjects (66 female, 28 male) were enrolled. Included were healthy subjects between the ages of 21 and 82 years without any history of vitreoretinal disease. Measurements were obtained with software from the OCT device. Significance was defined as a P value of less than .05. RESULTS: The mean age was 43.43 years ± 17.63 years. Correlation between decreasing CC flow density and increasing age was significant ( P < .001), with a mean yearly flow decrease of 0.026%. Subfoveal choroidal thickness decreased with advancing age; however, this did not reach a level of significance ( P = .069). CONCLUSION: There is a significantly negative correlation between CC flow density and advancing age in healthy subjects, analyzing direct extracted in-built software values from a commercial SD-OCTA device. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:302–308.]

Subretinal injection is a delicate and complex microsurgery, which requires surgeons to inject the therapeutic substance in a pre-operatively defined and intra-operatively updated subretinal target area. Due to the lack of subretinal visual feedback, it is hard to sense the insertion depth during the procedure, thus affecting the results of surgical outcome and hindering the widespread use of this treatment. This paper presents a novel approach to estimate the 3D position of the needle under the retina using the information from microscope-integrated Intraoperative Optical Coherence Tomography (iOCT). We evaluated our approach on both tissue phantom and ex-vivo porcine eyes. Evaluation results show that the average error in distance measurement is $4.7 \mu \text{m}$ (maximum of $16.5 \mu \text{m})$ . We furthermore, verified the feasibility of the proposed method to track the insertion depth of needle in robot-assisted subretinal injection.

Die Patienten entwickelten primar eine Visusminderung ein- bzw. beidseitig bei angiographisch und klinisch diagnostiziertem Papillenodem. Bei unauffalliger neurologischer und internistischer Abklarung bestatigte eine Serologie letztlich den Verdacht auf eine Papillitis bei akuter Syphilis. Eine Papillitis mit Visusminderung kann Symptom einer Syphilis sein. Man sollte hier nicht nur an die bekannte plakoide Chorioretinitis bei Lues denken. Eine ausfuhrliche Anamnese und diagnostische Masnahmen sind zur Ursachenfindung unerlasslich. Zielfuhrend sind meist auch das relativ junge Alter der Patienten, das mannliche Geschlecht, sexuelle Orientierung sowie fehlende klassische Risikofaktoren fur eine anteriore ischamische Optikusneuropathie (AION) oder neurologische Ursachen fur eine randunscharfe geschwollene Papille wie eine intrakranielle Raumforderung (Stauungspapille).

BACKGROUND AND OBJECTIVE: To investigate choriocapillary blood flow in myopic eyes using optical coherence tomography angiography. PATIENTS AND METHODS: Seventy-eight myopic and 79 age-matched healthy eyes were included in this study, with myopia defined as a spherical equivalent refraction (SER) between −1 diopters (D) and −6 D. Quantitative measurements of the choriocapillaris were obtained using the Avanti RTVue XR with AngioVue. Choroidal thickness (CT) was assessed using the single-line enhanced high-definition scan of the same device. RESULTS: CT correlated positively with SER ( P = .017) and negatively with bulbus axial length (AL) ( P = .180). Subfoveal choriocapillary blood flow did not show any significant correlation with any of the parameters SER, AL, or CT ( P = .798, P = .269, and P = .820, respectively). The mean flow signal of the myopic group did not differ significantly from the mean flow signal of the emmetropic control group ( P = .266). CONCLUSION: Choriocapillary blood flow seems to retain a constant level with increasing physiological myopia. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:e133–e139.]