Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel

No biomarker panel is established for prediction of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a major complication of allogeneic stem cell transplantation (alloSCT). We compared the potential of the Endothelial Activation and Stress Index (EASIX), based on lactate dehydrogenase, creatinine, and thrombocytes, with that of the SOS/VOD CIBMTR clinical risk score to predict SOS/VOD in two independent cohorts. In a third cohort, we studied the impact of endothelium-active prophylaxis with pravastatin and ursodeoxycholic acid (UDA) on SOS/VOD risk. The cumulative incidence of SOS/VOD within 28 days after alloSCT in the training cohort (Berlin, 2013-2015, n=446) and in the validation cohort (Heidelberg, 2002-2009, n=380) was 9.6% and 8.4%, respectively. In both cohorts, EASIX assessed at the day of alloSCT (EASIX-d0) was significantly associated with SOS/VOD incidence (p<0.0001), overall survival (OS) and non-relapse mortality (NRM). In contrast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiving pravastatin/UDA, the cumulative incidence of SOS/VOD was significantly lower at 1.7% (p<0.0001, Heidelberg, 2010-2015, n=359) than in the two cohorts not receiving pravastatin/UDA. The protective effect was most pronounced in patients with high EASIX-d0. The cumulative SOS/VOD incidence in the highest EASIX-d0 quartiles were 18.1% and 16.8% in both cohorts without endothelial prophylaxis as compared to 2.2% in patients with pravastatin/UDA prophylaxis (p<0.0001). EASIX-d0 is the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a prophylactic measure for patients at increased SOS/VOD risk

3D Heads-Up Display vs. Standard Operating Microscope Vitrectomy for Rhegmatogenous Retinal Detachment

Purpose: To assess the efficacy and outcomes of 23-gauge vitreoretinal surgery for rhegmatogenous retinal detachment using a three-dimensional heads-up display (3D HUD) surgical platform as compared to a standard operating microscope (SOM) setting. Design: Retrospective cohort study. Participants: One hundred and forty consecutive eyes of 140 patients with primary retinal detachment. Methods: All eyes underwent 23-gauge pars plana vitrectomy for primary retinal detachment using either a 3D HUD (NGENUITY;Alcon Inc., Fort Worth, Texas, USA;n = 70 eyes) or a SOM setting (n = 70 eyes);in cases of significant cataract, additional phacoemulsification with intraocular lens (IOL) implantation was performed. Minimum follow-up was 2 months. Main Outcome Measures: Primary retinal reattachment rate, rate of proliferative vitreoretinopathy (PVR), best-corrected visual acuity (BCVA), and duration of surgery. Results: There were 70 eyes each in the 3D HUD and the SOM group. Both groups did not differ concerning age (p = 0.70), extent of retinal detachment (p = 0.07), number of retinal tears (p = 0.40), macular involvement (p = 0.99), and preoperative BCVA (p = 0.99). Postoperatively, 3D HUD and SOM were comparable concerning the primary retinal reattachment rate (88.6 vs. 94.3%;p = 0.37), the development of postoperative PVR (12.9% vs. 7.1%;p = 0.40) and final BCVA (0.26 +/- 0.40 vs. 0.21 +/- 0.38 logMAR;p = 0.99). Duration of surgery was significantly longer in the 3D HUD group (66.2 +/- 16.5 vs. 61.2 +/- 17.1 min;p = 0.04), an effect which however vanished after a "learning curve" of the first 35 eyes (p = 0.49). Conclusions: On par results to a conventional operating microscope can be achieved with a 3D HUD setting when performing 23-gauge vitreoretinal surgery for rhegmatogenous retinal detachment, including the primary retinal reattachment rate, the incidence of postoperative PVR and final BCVA. However, duration of surgery might initially be slightly longer with 3D HUD, suggesting the effect of a learning curve

Intraocular Lens Power Calculation after Small Incision Lenticule Extraction

With more than 1.5 million Small Incision Lenticule Extraction (SMILE) procedures having already been performed worldwide in an ageing population, intraocular lens (IOL) power calculation in post-SMILE eyes will inevitably become a common challenge for ophthalmologists. Since no refractive outcomes of cataract surgery following SMILE have been published, there is a lack of empirical data for optimizing IOL power calculation. Using the ray tracing as the standard of reference - a purely physical method that obviates the need for any empirical optimization - we analyzed the agreement of various IOL power calculation formulas derived from the American Society of Cataract and Refractive Surgeons (ASCRS) post-keratorefractive surgery online calculator. In our study of 88 post-SMILE eyes, the Masket formula showed the smallest mean prediction error [-0.36 +/- 0.32 diopters (D)] and median absolute error (0.33D) and yielded the largest percentage of eyes within +/- 0.50D (70%) in reference to ray tracing. Non-inferior refractive prediction errors and +/- 0.50D accuracies were achieved by the Barrett True K, Barrett True K No History and the Potvin-Hill formula. Use of these formulas in conjunction with ray tracing is recommended until sufficient data for empirical optimization of IOL power calculation after SMILE is available

Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy

BACKGROUND To investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS Twenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography. RESULTS There were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60-72), total follow-up was 1.8 ± 0.4 (1-2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269-485) μm. After two years and 13 anti-VEGF injections on average, a mean reduction of - 39 ± 10 (- 26 to - 56) % to final 241 ± 52 (162-327) μm was observed (p~ 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r = - 0.79; R2~= 0.63; p~= 0.00073) and two (r = - 0.69; R2~= 0.48; p~= 0.019). While 85.7% of PNV eyes exceeded a pachychoroid threshold of ≥350 μm at baseline, this figure dropped to 21.4% at year one and 0% at year two. CONCLUSION In PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a \textquotedblvanishing pachy-choroid\textquotedbl, and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD

Improving morphological outcome in lamellar macular hole surgery by using highly concentrated autologous platelet-rich plasma

PURPOSE To evaluate the use of highly concentrated autologous platelet-rich plasma (PRP) in lamellar macular hole (LMH) surgery with regard to function and morphology. METHODS We included 12 eyes of 12 patients with progressive LMH in this interventional case series. After 23/25-gauge pars plana vitrectomy, 0.1ml highly concentrated autologous platelet-rich plasma was applied under air tamponade. Induction of posterior vitreous detachment and peeling of tractive epiretinal membranes were performed whenever present. Phacovitrectomy was undertaken in cases of phakic lens status. Postoperatively, all patients were instructed to rest in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, spectral-domain optical coherence tomography (SD-OCT), and fundus photography were carried out preoperatively and 6 months postoperatively. RESULTS Foveal configuration was restored in 10 of 12 patients (83.3%) at 6 months postoperatively. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (Wilcoxon: p=0.028). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p=0.67). No patient experienced vision loss after surgery, and no significant intra- or postoperative complications occurred. CONCLUSION The application of PRP in the surgical therapy of LMH results in good morphological and functional outcomes. Additional peeling of the ILM seems to be mandatory when using PRP to prevent the recurrence of LMH. Strict postoperative supine positioning for 2 h avoids PRP dislocation. Larger sample sizes are needed to confirm the results

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Background: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. Methods: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. Results: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. Conclusion: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance

On the need for an international effort to capture, share and use crystallization screening data

Development of an ontology for the description of crystallization experiments and results is proposed