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Purpose In bovine retinal pigment epithelium (RPE) cells, increased secretion of vascular endothelial growth factor (VEGF) has a positive linear association with proliferation of RPE. Spectral domain optical coherence tomography (SD-OCT) based improvement in grades of topographic retinal pigment epithelium alterations (RPE-A), were evaluated after intravitreal anti-VEGF therapy, in diabetic macular edema (DME), for the first time. Methods A tertiary care center-based, prospective study. Forty-four consecutive patients, 40–65 years of age with type 2 diabetes mellitus (DM) with DME, were administered three doses of anti-VEGF therapy at monthly intervals. Pre- and post-intervention SD-OCT was done and central sub field thickness (CST), cube average thickness (CAT) and topographic grades of RPE-A were assessed using single layer RPE map (SL-RPE) as; Grade 0: No alterations, Grade 1: Alteration in two quadrants, Grade 2: Alteration in more than two quadrants. Results CST decreased from 354.2 ± 16.0 µm pre-intervention to 233.2 ± 7.9 µm post-intervention. CAT reduced from 340.6 ± 6.5 µm pre-intervention to 274.1 ± 5.1 µm post-intervention. Significant improvement in grades of RPE-A pre- v/s post-intervention were observed. (Grade 0: 0 v/s 39; Grade 1: 17 v/s 3; Grade 2: 27 v/s 2) (p Conclusion Anti-VEGF therapy is associated with an improvement in grades of RPE-A in DME. The study was registered with the Clinical Trial Registry of India (CTRI/2019/03/018135).

Introduction The choice of surgical treatment for chronic, persistent and large full-thickness macular holes (FTMH) continues to be undefined and challenging, as some of these cases remain refractory to the treatment. We report the efficacy of combination of inverted internal limiting membrane flap technique (IILMFT) and subretinal application of the fluid (SR fluid application) technique for treatment of refractory FTMHs. Methods Nine patients (nine eyes) were enrolled into this retrospective non-randomized exploratory consecutive case series study. All patients were diagnosed with chronic, persistent or large FTMH and were treated with a combination of IILMFT and SR fluid application technique. The following outcome parameters were analysed during 1- and 6-month follow-up visits: anatomical FTMH closure rate on spectral domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), degree of postoperative retinal displacement. Results The mean preoperative diameter of FTMH was 542.0 μm (range 154–1930 μm). Final closure of FTMH was achieved in nine of nine cases (100%). In one case a second operation was required because of postoperative rhegmatogenous retinal detachment. The mean BCVA after the FTMH closure increased from 1.0 logMAR (0.7–1.3) to 0.4 logMAR (0.2–0.8 logMAR) (W = 2.67; p = 0.008). A positive correlation was revealed between preoperative BCVA and axial length (ρ = 0.67, p = 0.048), between preoperative BCVA and duration of the symptoms (ρ = 0.818, p = 0.007), as well as between postoperative BCVA at 1-month follow-up and BCVA at 6-month follow-up (ρ = 0.821, p = 0.007). Conclusion Combination of IILMFT with SR fluid application technique for refractory FTMH surgery appears to be effective and safe. Improvement of anatomical and visual outcomes after the single surgery benefits from and is ensured by the advantages of both novel surgical approaches. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00361-2.

In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce. The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS: Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed. No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure. The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction. Die Anlage eines transjugulären intrahepatischen portosystemischen Shunts ist ein etabliertes Verfahren in Patienten mit dekompensierter Leberzirrhose, es fehlen jedoch einheitlich Empfehlungen in der Patientennachsorge. Die Doppler-Sonografie wird regelhaft zur Kontrolle des Shunts genutzt. Aktuell gibt es keine Daten in Bezug auf elektive invasive Kontrollen. ZIEL: Ziel dieser retrospektiven Arbeit ist die Evaluation des Einflusses elektiver invasiver TIPS-Kontrollen in der Patientennachsorge. Es wurden Daten aller Patienten, die eine TIPS Implantation an den Universitätskliniken Münster und Bonn zwischen 2013 und 2018 erhalten haben, erhoben. Der Einfluss elektiver invasiver Kontrollen zwölf Monate nach TIPS Implantation bezüglich des Auftretens leber-assoziierter Ereignisse sowie der Häufigkeit von Shunt-Revisionen wurde analysiert. Es zeigten sich keine signifikanten Unterschiede bezüglich Leber-assoziierter Ereignisse nach 24 Monaten. Unterschiede bezüglich der Häufigkeit von Episoden hepatischer Enzephalopathien, einer Rekurrenz der initialen TIPS-Indikation, sowie Todesfällen oder Lebertransplantationen konnten nicht nachgewiesen werden. In einer Subgruppen-Analyse wurden nur Patienten, die innerhalb der ersten zwölf Monate kein leber-assoziiertes Ereignis oder eine TIPS-Revision hatten, analysiert: Auch hier wurden keine Unterschiede festgestellt. Unsere Daten zeigen keinen Vorteil für Patienten durch die Implementierung elektiver invasiver Kontrollen. Invasive Kontrollen sollten Patienten mit Hinweisen auf eine Shunt-Dysfunktion vorbehalten werden.

Background Cardiac involvement in liver cirrhosis in the absence of underlying cardiac disease is termed cirrhotic cardiomyopathy. The pathophysiology of this condition is still poorly understood. Purpose To investigate the extent of subclinical imaging changes in terms of fibrosis and inflammation and to explore the relationship between the severity of liver disease and the degree of myocardial involvement. Materials and Methods In this prospective study from November 2018 to December 2019, participants with liver cirrhosis and healthy control participants underwent hepatic and cardiac MRI. The multiparametric scan protocol assessed hepatic (T1 and T2 relaxation times, extracellular volume [ECV], and MR elastography-based liver stiffness) and cardiac (T1 and T2 relaxation times, ECV, myocardial edema, late gadolinium enhancement [LGE], and myocardial strain) parameters. Student t tests, one-way analysis of variance, Pearson correlation, and multivariable binary regression analysis were used for statistical analyses. Results A total of 42 participants with liver cirrhosis (mean age ± standard deviation, 57 years ± 11; 23 men) and 18 control participants (mean age, 54 years ± 19; 11 men) were evaluated. Compared with control participants, the participants with liver cirrhosis displayed reduced longitudinal strain and elevated markers of myocardial disease (T1 and T2 relaxation times, ECV, and qualitative and quantitative LGE). Myocardial T1 (978 msec ± 23 vs 1006 msec ± 29 vs 1044 msec ± 14; P < .001) and T2 relaxation times (56 msec ± 4 vs 59 msec ± 3 vs 62 msec ± 8; P = .04) and ECV (30% ± 5 vs 33% ± 5 vs 38% ± 7; P = .009) were higher depending on Child-Pugh class (A vs B vs C). Positive LGE lesions (three of 11 [27%] vs 10 of 19 [53%] vs nine of 11 [82%]; P = .04) were more prevalent in advanced Child-Pugh classes. MR elastography-based liver stiffness was an independent predictor for LGE (odds ratio, 1.6; 95% confidence interval: 1.2%, 2.1%; P = .004) and correlated with quantitative LGE (r = 0.67; P < .001), myocardial T1 relaxation times (r = 0.55; P < .001), and ECV (r = 0.39; P = .01). Conclusion In participants with liver cirrhosis, systolic dysfunction and elevated parameters of myocardial edema and fibrosis were observed at MRI, which were more abnormal with greater severity of liver disease. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by de Roos and Lamb in this issue.

BACKGROUND/OBJECTIVES: To study the mechanism of restoration of retinal photoreceptor ellipsoid zone (EZ), after intravitreal bevacizumab (IVB) therapy, in diabetic macular oedema (DMO). SUBJECTS/METHODS: Forty-four consecutive patients aged 40–65 years having type 2 diabetes mellitus (DM) with DMO were prospectively recruited for IVB therapy. It comprised of three doses (1.25 mg in 0.05 ml) of IVB at monthly intervals. Patients with other ocular and systemic diseases affecting retinal vessels and earlier ophthalmological interventions were excluded. Visual acuity (logMAR VA) was recorded. Spectral domain optical coherence tomography (SD-OCT) was performed pre and post intervention. Central sub-foveal thickness (CST) and grades of disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) and EZ were assessed. Data were statistically analysed on SPSS software. Clinical trials registry: CTRI/2019/03/018135. RESULTS: Mean logMAR VA decreased after IVB therapy from 1.78 ± 0.07 pre-intervention to 0.42 ± 0.05 post intervention (p

Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. The mean duration of the MH prior to SR-fluid application was 17 months (6–96 months). The mean age of the patients at the time of surgery was 72 years (54–88). The mean preoperative aperture diameter of the opening was 1212 μm (239–4344 μm), base diameter 649 μm (SD 320 μm). The mean preoperative BCVA prior to surgery was 0.1 (0.01–0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02–0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.

Zusammenfassung Einleitung Feste Adhäsionen zwischen der Netzhaut und dem angrenzenden retinalen Pigmentepithel (RPE) können das Verschließen von Makulalöchern (MH) nach der Chromovitrektomie verhindern. Die Anwendung von subretinaler Flüssigkeit (SR-Flüssigkeit) mit Balanced Salt Solution (BSS) kann diese Adhäsionen lösen und den Verschluss der zurückgezogenen Netzhaut unterstützen. Methoden Für ein standardisiertes Vorgehen empfiehlt es sich zunächst, die Netzhautoberfläche auf Reste von epiretinalen Membranen präoperativ am OCT oder intraoperativ mittels Vitalfarbstoffen auszuschließen. Intraoperativ appliziert man eine Blase schwerer Flüssigkeit über dem MH und senkt den Druck der Infusionsflasche auf Ergebnisse Mit einem standardisierten Vorgehen kann die Operation sicher und ohne Komplikationen durchgeführt werden. Maßnahmen wie Sorgfalt bei den luftfreien SR-Flüssigkeitsgaben oder maschinelle Assistenz wurden zusätzlich aufgenommen. In einer Pilotstudie führten erfahrene VR-Chirurgen die SR-Flüssigkeitsapplikation sicher und ohne Komplikationen durch. Der präoperative Durchmesser betrug 1150 µm (651 – 2350 µm). Die sekundäre Verschlussrate für unsere PMH betrug 80,9%. Schlussfolgerung SR-Adhärenzen scheinen bei persistierenden Makulaforamen eine bisher unbeachtete Komponente zu haben. Eine SR-Flüssigkeitsapplikation lässt sich sicher, schnell und mit minimalem Materialaufwand durchführen. Die initialen Ergebnisse zeigen eine hohe sekundäre Verschlussrate.

Background Vitamin D is a multi-functional fat-soluble metabolite essential for a vast number of physiological processes. Non-classical functions are gaining attention because of the close association of vitamin D deficiency with diabetes, and its complications. The present study was undertaken to evaluate the role of vitamin D as a biomarker for proliferative diabetic retinopathy. Methods A tertiary care center based cross-sectional study was undertaken. Seventy-two consecutive cases of type 2 diabetes mellitus were included. Diagnosis of diabetes mellitus was made using American Diabetes Association guidelines. Study subjects included: diabetes mellitus with no retinopathy (No DR) (n = 24); non-proliferative diabetic retinopathy (n = 24); and proliferative diabetic retinopathy (n = 24) and healthy controls (n = 24). All of the study subjects underwent complete ophthalmological evaluation. Best Corrected Visual Acuity (BCVA) was measured on the logarithm of the minimum angle of resolution (logMAR) scale. Serum 25-OH Vitamin D assay was done using chemiluminescent microparticle immunoassay technology. Diagnostic accuracy of vitamin D was assessed using receiver operating characteristics curve analysis and area under curve (AUC) was determined for the first time. Results ANOVA revealed a significant decrease in serum vitamin D levels with severity of diabetic retinopathy (F = 8.95, p p Conclusions Serum vitamin D levels of ≤ 18.6 ng/mL serve as sensitive and specific indicator for proliferative disease, among patients of DR.

Purpose To present the surgical treatment of a full thickness macular hole (MH) caused by a vitreomacular traction (VMT) on top of an adjacent subfoveal pigment epithelial detachment (PED) in age-related macular degeneration (AMD). Observation A 77-year-old female with a subfoveal PED receiving consecutive intravitreal injections noticed a sudden decreased visual acuity (VA) due to the development an occult MH in her right eye after 19 repeated intravitreal anti vascular endothelial growth factor (VEGF)-injections. Her initial VA declined from 20/50 to 20/400. The firm VMT induced a rupture of the multi-layered retina and may progress to an RPE-tear or possible to a subretinal haemorrhage. We discussed with the patient the risks of the natural progression and explained possible treatment options: We continued her anti-VEGF combined with air bubble injections to induce a posterior vitreous detachment, to stabilise the retinal architecture, reduce the subretinal fluid and avoid possible intraoperative bleeding. As injections did release the VMT, vitrectomy released the posterior vitreous from the optic nerve and trimmed it towards the central retina. Peeling with brilliant blue removed the internal limiting membrane without any signs of bleeding, rupture of the PED or enlargement of the MH, prior to the installation of 10% SF6 gas. The postoperative optical coherence tomography (OCT) on day 5 confirmed a closed MH, while the size, shape and pattern of the PED remained unchanged. Her VA increased from 20/400 to 20/50 (equal to her previous VA prior to the MH-formation). To avoid a potential progression of the PED, we maintained her retreatment intervals at 5 weeks for the next 6 months. A literature review presents similar intraoperative approaches and postoperative outcomes in 8 out of the 9 published cases. Conclusions and importance VMT can induce an occult MH on top of a PED, causing a significant loss of vision. When gas injections are not successful, surgery may release the traction, restore the retinal architecture, and significantly improve and maintain the VA over a documented long-term observation. The epiretinal procedure should be assisted under regular anti-VEGF injections to maintain the subretinal architecture.

The external limiting membrane (ELM) and ellipsoid zone (EZ) can be observed exquisitely by SD-OCT. In diabetic macular edema (DME), dysfunction of mitochondria, represented by the EZ in the foveal photoreceptors results in reduced visual acuity (VA). An increase in VEGF was found to correlate with increased severity of DR, increased central subfield thickness (CST), and sequential disruption of ELM and EZ. The mechanism of ELM and EZ restoration after anti-VEGF therapy in DME has been discovered. The ELM restores first followed by EZ restoration. Thus, authors have discovered and established ELM as a novel retinal structural barrier.

PURPOSE To evaluate the 52-week safety and efficacy of intravitreal ziv-aflibercept in patients with neovascular age-related macular degeneration. METHODS All patients received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (1.25 mg) followed by a pro re nata regimen. The best-corrected visual acuity and spectral domain optical coherence tomography were obtained at baseline and monthly. Full-field and multifocal electroretinograms were obtained at baseline and 4, 13, 26, and 52 weeks. For some full-field electroretinography parameters, we calculated the differences between baseline and 52 weeks and then compared those differences between treated and untreated fellow eyes. RESULTS Fifteen patients were included and 14 completed the 52-week follow-up. The mean best-corrected visual acuity improved from 0.95 ± 0.41 (20/200) at baseline to 0.75 ± 0.51 (20/125) logarithm of the minimum angle of resolution at 52 weeks (P = 0.0066). The baseline central retinal thickness decreased from 478.21 ± 153.48 μm to 304.43 ± 98.59 μm (P = 0.0004) at 52 weeks. Full-field electroretinography parameters used to assess retinal toxicity after intravitreal injections (rod response and oscillatory potentials) remained unchanged during follow-up. The average multifocal electroretinography macular response in 5° showed increased N1-P1 amplitude and decreased P1 implicit time (P < 0.05). One patient presented with intraocular inflammation after the seventh intravitreal procedure. CONCLUSION The results suggested that intravitreal ziv-aflibercept might be safe and effective for treating neovascular age-related macular degeneration. More patients and a longer follow-up are needed to confirm the long-term outcomes of intravitreal ziv-aflibercept.

BACKGROUND & AIMS: Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced cirrhosis and acute decompensation is unclear and investigated in this study.METHODS: Patients with decompensated cirrhosis from the prospective NEPTUN cohort (ClinicalTrials.gov Identifier: NCT03628807), who underwent transjugular intrahepatic portosystemic shunt procedure were included. Clinical and laboratory parameters, PRO-C4 and C4M levels were measured in blood samples from portal and hepatic veins just before transjugular intrahepatic portosystemic shunt placement.RESULTS: Levels of C4M and PRO-C4 are significantly lower in patients with massive ascites and impaired renal sodium excretion. C4M and PRO-C4 show gender-specific profiles with significantly lower levels in females compared to males. Females with higher C4M levels show higher mortality. By contrast, males with higher C4M levels show lower mortality. In multivariate Cox regression analysis, C4M is an independent predictor of survival in female patients.CONCLUSION: This study shows that markers of collagen type IV remodelling do not accumulate in severe renal dysfunction. Although collagen type IV degradation markers derive from the liver, portal venous C4M levels are relevant for survival. Moreover, it demonstrates that circulating C4M shows gender-specific profiles, which can independently predict survival in female patients with decompensated cirrhosis.

Purpose To evaluate AngioJet-assisted transvenous portal vein (PV) thrombectomy for non-cirrhotic patients with total portal vein and mesenteric vein thrombosis (PVMVT). Material and methods From 2015 to 2016 four patients (3 male, mean 43.9 years, range 33-52 years) with acute (3 cases) and acute-on-chronic (1 case) PVMVT underwent transvenous thrombolysis. All patients received initial AngioJet (Boston Scientific, Natick, MA, USA) thrombectomy followed by continuous catheter directed thrombolysis with Urokinase (Medac, Wedel, Germany) for 22-52 hours. Transjugular intrahepatic portosystemic shunts (TIPS), using Viatorr stent grafts (W.L. Gore and Associates, AZ, USA; mean diameter: 10 mm, length: 60-80 mm), were implanted in all patients. Patients were followed clinically and with imaging (mean 646 days, range 392 to 936 days). Results Technical success was 100%. Therapeutic success was achieved in 75% of cases. AngioJet-assisted thrombectomy substantially reduced thrombus load in the acute cases, while only slight improvement was achieved in the acute-on-chronic case. Continuous thrombolysis subtotally re-established PV flow in the acute cases, while only minimal improvement was seen in the acute-on-chronic case. Following TIPS implantation complete PV recanalisation could be achieved in all acute cases. In the acute-on-chronic case initial stagnant PV flow was seen; however, PV and TIPS re-occluded 10 days after implantation. During follow-up PV remained patent in acute cases. Conclusions AngioJet-assisted thrombectomy was technically feasible and uncomplicated in all of our patients. The initial results suggest that AngioJet-assisted thrombectomy facilitates recanalisation in acute and severe cases of PVMVT.

Background To evaluate the association of central subfield thickness (CST) and cube average thickness (CAT) with ellipsoid zone (EZ) disruption on spectral domain optical coherence tomography (SD-OCT) in patients of diabetic retinopathy (DR). Methods Cross sectional study including consecutive patients of type 2 diabetes mellitus [without DR (No DR, n = 97); non-proliferative DR (NPDR, n = 91); proliferative DR (PDR, n = 83)] and healthy controls (n = 82) was undertaken. CST and CAT values were measured using SD-OCT. Data was analyzed using Chi square test, ANOVA and multivariate analysis. Discriminant values of CST and CAT for EZ disruption were evaluated using receiver operator characteristic curve. Area under curve (AUC) was computed. Results Mean CAT and CST values in the study subjects showed an incremental trend. Multivariate ordinal logistic regression analysis showed increase in CST (OR = 1.022, p

Cortisol, a steroid hormone, plays an essential role in metabolic processes of diabetes mellitus. This study for the first time evaluated the association of serum cortisol with spectral domain optical coherence tomography (SD-OCT)-based cross-sectional and topographic parameters with severity of diabetic retinopathy (DR). A tertiary care center-based preliminary study was undertaken. Fourteen consecutive cases of DR and fifteen healthy controls were included. Cases were graded according to ETDRS classification: non-proliferative DR (NPDR, n = 8) and proliferative DR (PDR, n = 6). All study subjects underwent complete ophthalmological evaluation. Serum cortisol was analyzed using chemiluminescence microparticle assay method. Central subfield thickness (CST), cube average thickness (CAT), cube volume (CV), retinal nerve fiber layer (RNFL) thickness, disorganization of inner retinal layers (DRIL), grade of retinal photoreceptor ellipsoid zone (EZ) disruption and grade of retinal pigment epithelium (RPE) alterations were evaluated using SD-OCT. Statistical analysis was done using ANOVA and Pearson’s correlation analysis. Mean serum cortisol levels (µg/dL) were NPDR = 11.59 ± 0.42, PDR = 14.50 ± 0.26 and controls = 8.22 ± 0.77. With increasing severity of DR, mean CST, CAT, CV showed positive correlation, whereas mean RNFL thickness showed negative correlation with serum cortisol levels (p

Background Anti-angiogenic drugs remain the mainstay therapy for several vascular retinal pathologies. The repurposing of approved anti-angiogenic drugs for use in ophthalmology can increase therapeutic options and reduce costs. The purpose of this study was to investigate the ocular safety profile of intravitreal (IVT) ramucirumab, an approved anti-vascular endothelial growth factor molecule for systemic treatment, using cell culture and animal models. Methods The cytotoxicity of ramucirumab at different concentrations was evaluated in human retinal pigment epithelial cells (ARPE-19) using the MTT assay. In addition, 250 or 500 µg of ramucirumab or vehicle was injected in the eye of 16 chinchilla rabbits. The eyes were evaluated by ophthalmoscopy, electroretinography, spectral-domain optical coherence tomography (SD-OCT) and by light and transmission electron microscopy. Results Electroretinography or SD-OCT did not detect functional or morphological alterations at 24 h or one week after injection. Light and transmission electron microscopy confirmed the absence of major signs of toxicity, although we found a statistically significant reduction in ganglion cell number between the controls and the eyes that received 500 µg of ramucirumab after 7 days. Compared to lower concentrations, 500 µg of ramucirumab caused reduction in cell viability and changes in morphology in ARPE-19 cells. Compared to the baseline, ocular and serum osmolarity showed no difference after IVT injection at all timepoints. Conclusion In conclusion, IVT injection of ramucirumab in rabbits is safe and does not cause functional damage to the retina. At the lower dose tested in vivo (250 µg), the morphology and ultrastructural anatomy were normal at 24 h and 1 week after the injection. However, the 500 µg dose can cause a decrease in ganglion cell number seven days after the injection.

The purpose of this article is to review the literature on nomenclature, natural history, clinical features, diagnosis, management, and prognosis of both macular microhole (MMH) and foveal red spot syndrome (FRS).A PubMed primary literature search (February 1, 2020) utilizing the terms macular microhole, foveal red spot syndrome, and outer retinal hole was conducted. All chosen articles were case reports or case series. Articles qualified for inclusion if they documented symptoms, imaging findings, or followed patients longitudinally.A total of 14 studies from 1988 to 2019 that evaluated either MMH, FRS, or both were included in the review. No comparative study between the two defects was found. Studies often used the terms FRS and MMH interchangeably to reference both partial- and full-thickness lesions of the macula. Spectral-domain optical coherence tomography (SD-OCT) was most frequently able to identify these lesions and revealed an absence of all neural retinal layers from the inner limiting membrane (ILM) to the retinal pigment epithelium (RPE) in the full-thickness lesions while the partial-thickness lesions most often involved the photoreceptor layer (PRL) and less frequently the external limiting membrane (ELM). OCT revealed that vitreomacular traction (VMT) was involved in the natural history of both FRS and MMH for a significant subset of patients.The terms MMH and FRS have been used interchangeably in the literature. Advances in OCT have revealed that MMHs and FRSs are distinct but sometimes overlapping entities. We suggest that MMH and FRS are similar entities defined as one or more sharply defined lesions in the fovea of the eye 150 μm in size. MMHs are a full-thickness defect of the entire neuroretina at the center of the foveola while FRSs are partial-thickness lesions. Current literature suggests that there may be subtle differences in the pathogenesis, clinical features, and diagnosis between MMH and FRS; however, prognosis and management for both are favorable. Lastly, we suggest that the terms outer lamellar macular microholes and full-thickness macular microholes may be the more appropriate terminologies to refer to FRS and MMH, respectively.

Firm adhesions between the retina and adjacent retinal pigment epithelium (RPE) may prevent the closure of macular holes (MH) after chromovitrectomy. Controlled application of subretinal (SR) fluid with BSS may release these adhesions leading to closure of the retracted retina in large and or refractory macular holes.For a standardized procedure, it is recommended to exclude residues of epiretinal membranes on the retinal surface preoperatively at OCT or intraoperatively by means of vital dyes. Intraoperatively, a perfluorocarbon (PFO) bubble is placed above the MH and lowers the infusion bottle of 20 mmHg. Subsequently, SR-fluid blebs are applied in the upper, temporal and inferior quadrants with a subretinal 41-gauge cannula. After removing decalin bubble, the SR-detachment is enlarged toward the foveal center. This is essential to achieve a complete detachment of the outer macular edges from the RPE. The MH can be closed by a temporary gas endotamponade.With a standardized procedure, the operation can be carried out safely and with minimal effort. Additional measures, such as care for bubble-free SR-fluid sands or machine assistance, were added. In a pilot study, experienced VR surgeons performed the SR-fluid application safely and without complications. The preoperative diameter of the MH was 1150 µm (651 - 2350 µm). The secondary closure rate for our PMH was 80.9%.SR-adhesions seem to have a previously unnoticed component in persistent macular holes. An SR-fluid application can be carried out quickly, safely and with minimal material effort. The initial results show a high secondary closure rate.Feste Adhäsionen zwischen der Netzhaut und dem angrenzenden retinalen Pigmentepithel (RPE) können das Verschließen von Makulalöchern (MH) nach der Chromovitrektomie verhindern. Die Anwendung von subretinaler Flüssigkeit (SR-Flüssigkeit) mit Balanced Salt Solution (BSS) kann diese Adhäsionen lösen und den Verschluss der zurückgezogenen Netzhaut unterstützen.Für ein standardisiertes Vorgehen empfiehlt es sich zunächst, die Netzhautoberfläche auf Reste von epiretinalen Membranen präoperativ am OCT oder intraoperativ mittels Vitalfarbstoffen auszuschließen. Intraoperativ appliziert man eine Blase schwerer Flüssigkeit über dem MH und senkt den Druck der Infusionsflasche auf 20 mmHg. Danach werden SR-Flüssigkeitsbläschen im oberen, temporalen und inferioren Quadranten mit einer subretinalen 41-G-Kanüle angelegt. Nach Entfernen der schweren Flüssigkeit wird die SR-Abhebung in Richtung Zentrum vergrößert. Es ist notwendig, eine vollständige Ablösung der inneren und äußeren Makulakanten vom RPE zu erzielen. Mit einer temporären Gastamponade kann das MH verschlossen werden.Mit einem standardisierten Vorgehen kann die Operation sicher und ohne Komplikationen durchgeführt werden. Maßnahmen wie Sorgfalt bei den luftfreien SR-Flüssigkeitsgaben oder maschinelle Assistenz wurden zusätzlich aufgenommen. In einer Pilotstudie führten erfahrene VR-Chirurgen die SR-Flüssigkeitsapplikation sicher und ohne Komplikationen durch. Der präoperative Durchmesser betrug 1150 µm (651 – 2350 µm). Die sekundäre Verschlussrate für unsere PMH betrug 80,9%.SR-Adhärenzen scheinen bei persistierenden Makulaforamen eine bisher unbeachtete Komponente zu haben. Eine SR-Flüssigkeitsapplikation lässt sich sicher, schnell und mit minimalem Materialaufwand durchführen. Die initialen Ergebnisse zeigen eine hohe sekundäre Verschlussrate.

Background: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). Methods: This prospective, observational study enrolled 65 patients with acute (

Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p 83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS., Jonel Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57, CRC1382), Cellex Foundation and European Union’s Horizon 2020 research and innovation program GALAXY study (No. 668031), LIVERHOPE (No. 731875) and MICROB-PREDICT (No. 825694) and the Cellex Foundation. Joan Genescà is a recipient of a Research Intensification grant from Instituto de Salud Carlos III, Spain. The study was partially funded by grants PI15/00066, and PI18/00947 from Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivasis supported by Instituto de Salud Carlos III. Macarena Simón-Talero is a recipient of the grant JR 17/00029 from Instituto de Salud Carlos III

Iliocaval obstruction is a substantial contributor to chronic venous insufficiency and is increasingly being treated endovascularly with angioplasty and stent placement. Utilization of an appropriate stent for treatment is pivotal; however, until today, mechanical properties of venous stents remain unknown. We analyzed the radial resistive force, the chronic outward force, as well as the crush resistance of seven stent models [Zilver Vena (Cook, Bjaeverskov, Denmark), Sinus Venous, Sinus Obliquus and Sinus XL Flex (Optimed, Ettlingen, Germany), Vici (Veniti; St. Louis, USA), Wallstent (Boston Scientific, Marlborough, USA), and Venovo (Bard, Tempe, USA)] in vitro using a radial force testing machine (RX-650, Machine Solutions Inc., Flagstaff, AZ, USA) and a hardness testing machine (zwickiLine, Zwick Roell, Ulm, Germany). The Sinus Obliquus revealed the highest radial resistive force (19.41 N/cm) and the highest chronic outward force at 50 and 30% nominal diameter (7.93 N/cm at 50%, 16.97 N/cm at 30%) while the Venovo revealed the highest chronic outward force at 90 and 80% nominal diameter (4.83 N/cm at 90%, 5.37 N/cm at 80%). The radial resistive force and the chronic outward force of the Wallstent greatly depended on whether the stent ends were fixated. The Wallstent revealed the highest crush resistance at nominal diameters of 90% (0.46 N/cm) to 60% (1.16 N/cm). The Sinus Obliquus revealed the highest crush resistance at a nominal diameter of 50% (1.41 N/cm). Venous stents greatly differ regarding their mechanical properties. These results should be considered when choosing an appropriate stent for the treatment of venous obstruction.

PURPOSE To evaluate the impact of the vitreoretinal interface architecture, in specific the angle between the posterior vitreous cortex and the internal limiting membrane, on vitreomacular traction (VMT) resolution in eyes treated with intravitreally injected ocriplasmin (Jetrea). METHODS Retrospective, multicenter cohort study and exploratory data analysis. Spectral domain optical coherence tomography assessments were performed before scheduled ocriplasmin injections. General (age and sex) as well as ocular variables (lens status, presence of epiretinal membrane formations, horizontal diameter of VMT, central retinal thickness, and in particular various prespecified angles between the posterior vitreous cortex and internal limiting membrane) were analyzed to evaluate their impact on successful VMT resolution. RESULTS Fifty-nine eyes of 59 patients were included. Univariate analysis of age (odds ratio [OR]: 0.881; 95% CI: [0.812-0.955]; P = 0.0022) and lens status (OR: 11.03; 95% CI: [2.23-54.57]; P = 0.0033) had a significant impact on successful VMT resolution, whereas sex (OR: 0.668; 95% CI: [0.126-2.065]; P = 0.4906), epiretinal membrane formation (OR: 0.581; 95% CI: [0.168-2.006]; P = 0.3903), horizontal diameter of VMT (OR: 0.99930; 95% CI: [0.99825-1.00035]; P = 0.1886), and central retinal thickness (OR: 0.9985; 95% CI: [0.9934-1.00436]; P = 0.56) failed. The angle at 500 μm apart from the fovea centralis, irrespective if measured nasally (OR: 1.135; 95% CI: [1.013-1.272]; P = 0.0289) or temporally (OR: 1.099; 95% CI: [1.001-1.208]; P = 0.0485), showed a significant correlation with VMT resolution. CONCLUSION The angle between the posterior vitreous cortex and the internal limiting membrane 500 μm apart from the fovea centralis correlates with VMT resolution and may be a clinically useful marker for selection of patients to be treated with ocriplasmin. This observation needs to be proven in a prospective confirmatory investigation.

ZusammenfassungDie Einengung des Kammerwinkels durch anatomische Prädisposition – z. B. bei hoher Hyperopie oder durch zunehmende Dicke der kristallinen Linse – stellt den größten Risikofaktor für einen akuten Winkelblock dar. Während die Anlage einer Iridotomie zur Durchbrechung eines akuten Winkelblocks eine Standardprozedur darstellt, gibt es bisher keine einheitlichen Empfehlungen oder Leitlinien für eine prophylaktische Therapie. Moderne bildgebende Verfahren wie die optische Kohärenztomografie oder computergestützte Scheimpflug-Fotografie können bei der Therapieentscheidung wertvolle Informationen liefern. In der vorliegenden Übersicht werden traditionelle wie moderne Untersuchungstechniken vorgestellt und die sich aus den Ergebnissen erster Studien abgeleiteten Handlungsempfehlungen zusammengefasst.