Tumor Control Probability and Time-Dose Response Modeling for Stereotactic Radiosurgery of Uveal Melanoma.

INTRODUCTION: Uveal melanoma (UM), while a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiotherapy. This study seeks to elucidate the significance of the prescription dose by employing time-dose response models for UM patients receiving photon-based stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Inclusion criteria comprised UM patients treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into three dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose response models for LC were created at 2, 4, and 7 years using maximum-likelihood fitted logistic models. RESULTS: Outcomes from 594 patients with 594 UM were used to create time-dose response models. The prescribed doses and the number of patients were as follows: 17-19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For four years and a LC of 90%, a dose of approximately 21 Gy was required. After seven years, the 21 Gy prescription dose is predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. CONCLUSION: In contrast to prior findings, the time-dose response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly.

Long-Term Results of 0.19mg Fluocinolone Acetonide Insert for Treatment of Non-Infectious Uveitis in Clinical Practice.

PURPOSE: To evaluate the long-term outcomes of patients with non-infectious uveitis treated with 0.19 mg fluocinolone acetonide insert (FAi) for up to 36 months in clinical practice. METHODS: A retrospective study conducted at a single uveitis center. RESULTS: Fifty eyes of 39 patients were included. Mean best corrected visual acuity (BCVA) and central retinal thickness (CRT) remained stable until month 36 after FAi implantation (61.04 vs. 70.25 letters and 370.8 vs. 332.5 µm, respectively). The recurrence rate was 34% (17 eyes) after 36 months, of which 82% (14 eyes) received high-dose corticosteroids before FAi. Mean intraocular pressure (IOP) remained unchanged (13.38 vs. 15.74 mmHg), while most phakic eyes (13 of 14 eyes) required cataract surgery. CONCLUSIONS: We show that FAi effectively prevents recurrences of non-infectious uveitis for up to three years in clinical practice, comparable with randomized clinical trials. Patients who received high-dose corticosteroids before FAi have an increased risk for early recurrence and should be considered for scheduled re-treatment.

Local Recurrence in Choroidal Melanomas following Robotic-Assisted Radiosurgery (CyberKnife).

Introduction: Tumor recurrence in choroidal melanoma has been associated with decreased overall survival due to metastatic spreading. To detect risk factors of local recurrence and side effects, we analyzed tumor planning and treatment parameters in patients with recurrence of choroidal melanoma after treatment with robotic-assisted radiosurgery (CyberKnife). Methods: Six hundred ninety-four patients treated with CyberKnife between 2005 and 2019 were retrospectively reviewed. Age, gender, best-corrected visual acuity, tumor height, and diameter were recorded. Treatment planning and radiation doses were reviewed. Salvage therapy, overall survival, metastasis, and complications were recorded. Results: Seventy-four patients showed local recurrence. Local recurrence occurred after 42.1 months post CyberKnife treatment (mean; range: 5-100 months). Fourteen out of 74 patients (18.9%) died during follow-up. Recurrence treatment included enucleation in 51 patients (68.9%) and radiosurgery in 19 patients (25.7%). Treatment planning without contrast medium MRI, radiation dose of less than 21 Gy, and insufficient margin delineation were identified as risk factors incrementing local control. Discussion: Robotic-assisted radiosurgery (CyberKnife) is a suitable treatment option for large choroidal melanoma up to 12 mm. Patients with significantly better visual acuity received repeat CyberKnife treatment as salvage therapy and showed an eye retention rate of 81%.

Robotic CyberKnife Radiosurgery for the Treatment of Choroidal and Ciliary Body Melanoma.

PURPOSE: To present the results of robotic-assisted radiosurgery in choroidal and ciliary body melanomas treated at the Department of Ophthalmology of Ludwig-Maximilians-University and the European CyberKnife Center in Munich, Germany. DESIGN: Interventional case series METHODS: This retrospective study included 594 consecutive patients referred to our clinic for the treatment of choroidal and ciliary body melanomas with robotic radiosurgery (CyberKnife) from 2005 to 2019. Eye retention, local control and disease-specific survival rates were calculated as Kaplan-Meier and actuarial estimates. The impact of prescription dose, tumor size, and ciliary body involvement was assessed by likelihood ratio tests and Cox regression. RESULTS: Among all patients who were staged according to the TNM classification system (8th edition), 22.7% were I, 57.9% were II, 18.9% were III, and 0.5% were IV. Median apical tumor height and base diameter were 5.8 and 11.4 mm. The mean follow-up was 41.7 months. Local control after 3 and 5 years was 92.0% (95% CI = 88.2%-94.7%) and 84.3% (95% CI = 77.9%-89.0%), respectively, for 21 to 22 Gy and 86.9% (95% CI = 79.7%-91.7%) and 77.7% (95% CI = 68.5%-84.6%), respectively, when treated with 20 Gy or less. Eye retention was achieved in 89.9% and 81.0% after 3 and 5 years with 21 to 22 Gy and 85.9% and 80.0% for 20 Gy or less. Disease-specific survival rates were 93.1% (95% CI = 90.2%-95.2%) after 3 years, 89.8% (95% CI = 86.0%-92.6%) after 5 years, and 87.8% (95% CI = 82.8%-91.4%) after 7 years. CONCLUSIONS: This is the largest series of patients treated for choroidal and ciliary body melanomas with CyberKnife. Our results reflect an improvement in the outcome of CyberKnife therapy for patients with choroidal and ciliary body melanoma treated with single-session radiosurgery in the last decade.

Pars-plana-vitrectomy for endophthalmitis treatment and the role of standardized ultrasound.

PURPOSE: Endophthalmitis is a severe inflammation following surgery or endogenous spread of pathogens. Besides clinical signs and symptoms, standardized ultrasound might help to confirm the diagnosis. Thus, we analyzed 172 cases of endophthalmitis for pathogens, visual acuity (VA) and the predictive value of standardized ultrasound. METHODS: Retrospective analysis of patients treated with pars-plana-vitrectomy for endophthalmitis at the University Eye Hospital was performed. Sex, age, VA at presentation, first day after surgery, four weeks postoperatively, and at last follow-up, as well as pathogen culture, and presence of standardized ultrasound before vitrectomy were recorded. Mann-Whitney U and Chi-square tests were used for groupwise comparisons. RESULTS: A total of 172 patients (male = 47.7%) with a median age of 76 years (IQR 65-82 years) treated for endophthalmitis (exogenous = 85.5%) were included. Median follow-up time was 65 days (IQR 12-274 days). Visual acuity at presentation was 2.30 logMAR (IQR 2.70-2.30 logMAR); it increased to 1.00 logMAR (1.4-0.40 logMAR) at last follow-up. A total of 79 patients (45.9%) underwent standardized ultrasound before vitrectomy. Patients with positive ultrasound criteria had a significantly decreased VA at presentation (p = 0.034). Positive microbiological cultures for Streptococcus spp. and Enterococcus faecalis were associated with decreased VA (p = 0.028) at last follow-up. CONCLUSION: Standardized ultrasound is an easy and robust tool in the diagnosis of endophthalmitis. Positive criteria are significantly associated with decreased VA at presentation. The recovery of VA depends on pathogens and is significantly worse for certain species (Streptococcus spp., Enterococcus faecalis).

Differences in beginner and expert neurointerventionalists" heart rate variability during simulated neuroangiographies.

BACKGROUND: Likewise work experience, heart rate variability (HRV) has repeatedly been correlated with improved performance under real life and simulator conditions. Using HRV as a correlate of workload, it is meaningful to assess the impact of work experience. To understand the impact of work experience on HRV metrics, we examined differences in HRV among experts and beginners during simulated endovascular neuroradiological procedures. METHODS: Six inexperienced radiologists (beginners) and five experts in neurological endovascular intervention each performed 10 diagnostic angiographies on a Vascular Interventional System Trainer (VIST) simulator (Mentice AB, SW). Beyond total time, fluoroscopy time, and amount of contrast medium used, heart rate variability and the NASA-task load index were gathered as correlates of workload. The t-Test for independent samples as well as Mann-Whitney-U tests were applied for group-wise comparison between beginners and experts. Multivariate regression was used to assess the influence of age and expert status. RESULTS: Ten participants completed all scenarios; one participant only completed the first five scenarios. Accordingly, 105 simulations were analyzed (beginners N = 60; experts N = 45, respectively). The heart rate variability of experts and beginners significantly differed in three time domain HRV metrics (decreased RMSSD, NN50, pNN50 in experts; all p < 0.05) as well as with respect to its distribution in the frequency spectrum (LF/HF ratio; p < 0.001, increased high frequency components in experts). CONCLUSIONS: The HRV of beginners and expert neurointerventionalists significantly differed during simulated endovascular neuroradiological procedures. Experts presented decreased HRV, this could be a cardiovascular surrogate to the effort the subjects expend on their performance. It is in line with previous studies on vagal influences on the heart and cognitive-executive performance.

Robotic CyberKnife radiosurgery for small choroidal melanomas.

Plaque brachytherapy is the most common procedure for the treatment of small choroidal melanoma, especially in posteriorly located tumors. However, there is only little information on outcome after treatment with stereotactic radiosurgery, for example, CyberKnife radiosurgery. We reviewed patients with choroidal melanoma (maximum tumor height 4 mm) treated with CyberKnife radiosurgery. Demographic information, tumor dimension, complications, metastasis and overall survival during the whole follow-up were tracked and analyzed with a specific focus on local tumor control and potential risk factors. One hundred eighty-eight patients (102 female, 54.2%) with a median age of 63 years [interquartile range (IQR): 54-73 years] were analyzed over a median of 46 months (IQR: 24-62 months). Metastasis occurred in 14 patients (7.4%) in median of 18 months after treatment (IQR: 13-47 months) and survival was achieved in 178 patients (94.7%). Within the observation period, eye retention was observed in 166 patients (88.3%). Superior local control was achieved in patients who received a prescription dose of at least 21 Gy or more (91.6%; P = 0.04). Other potential risk factors incrementing local control were treatment planning with missing MRI in advance and too small target delineation during the planning process. Radiosurgery (CyberKnife) in a single, outpatient procedure is suitable for the treatment of small choroidal melanoma. We found local control rate after 3 years compared to the standard treatment with plaque brachytherapy. On the study side, 15 years of CyberKnife treatment allowed to identify risk factors that might increment local control and thus improve treatment regimens.

Effects of the First COVID-19 Lockdown on Ophthalmological Patient Care.

PURPOSE: To determine the effect of lockdown on medical care, with the example of ophthalmology. METHODS: Patients in a period during the first lockdown were compared to a non-lockdown period, with a total of 12 259 patients included in an observational study. Changes in different areas (elective, emergency, inpatients, surgeries) and eye care subspecialties were compared. Emergency patients were analyzed according to severity and urgency. Patients showing hints requiring treatment for urgent cardiovascular diseases were determined. Differences in patients who would have suffered severe vision loss without treatment were identified and the QALY (quality-adjusted life years) loss was determined accordingly. A model to prioritize patient visits after the end of lockdown or in future lockdown scenarios was developed. Data were collected at the University Eye Hospital LMU Munich and patient files were reviewed individually by ophthalmologists. RESULTS: The average patient number decreased by - 59.4% (p < 0.001), with a significant loss in all areas (elective, emergency, inpatients, surgeries; p < 0.001). There was a decline of - 39.6% for patients at high risk/high severity. Patients with indications of a risk factor of future stroke declined significantly (p = 0.003). QALY loss at the university eye hospital was 171, which was estimated to be 3160 - 24 143 for all of Germany. Working up high losses of outpatients during these 8 weeks of projected lockdown in Germany would take 7 - 23 weeks under normal circumstances, depending on ophthalmologist density. The prioritization model can reduce morbidity by up to 78%. CONCLUSION: There was marked loss of emergency cases and patients with chronic diseases. Making up for the losses in examinations and treatments will theoretically take weeks to months. To reduce the risk of morbidity, we recommend a prioritization model for rescheduling and future lockdown scenarios.

Robotic assisted CyberKnife radiosurgery for the treatment of iris melanoma.

Iris melanoma is a rare form of uveal melanoma with potential metastic spread. Treatment options include surgical resection, enucleation or irradiation. We analysed visual outcome, complication appearance and management in eight patients with iris melanoma following robotic-assisted CyberKnife treatment. Consecutive patients from the Department of Ophthalmology at University of Munich were included in the study if they had an iris melanoma that was treated with CyberKnife and had a minimum follow-up of 12 months. We evaluated tumor thickness, largest diameter, visual acuity and complications. 8 patients were included in this report. The median age was 74 years (range: 53-86 years). The median follow-up was 23 months (range 12-48 months). Tumor thickness decreased from 2.1 to 1.4 mm on average. Four out of eight patients showed stable or increased visual acuity compared to visual acuity at first visit. We did not find a correlation of applied radiation volume or radiation dose on visual outcome. Radiation keratopathy was the most common complication in five patients. No recurrences were noted. Robotic-assisted radiosurgery following CyberKnife is a promising non-invasive, single session treatment option for iris melanoma with comparable results regarding recurrence rate or complications to brachytherapy and proton beam therapy. All included patients showed good visual outcome.

Robotic assisted CyberKnife radiosurgery for the treatment of choroidal metastasis.

PURPOSE: Choroidal metastases occur in many patients with systemic cancer and limit quality of life due to visual deterioration or pain. The limited prognosis of these patients demand treatment approaches that aim at a quick response and easy application. We evaluated a robotic assisted radiosurgery device, the CyberKnife, in the treatment of choroidal metastasis. METHODS: Following retrobulbar anaesthesia, target volume was defined by an interdisciplinary team using gadolinium-contrast-enhanced MRI, computer tomography (CT) as well as all previously obtained clinical data. Radiation was delivered in a single fraction with a CyberKnife at a radiation dose of 21 Gy with a 70% isodose. We evaluated tumour height, reflectivity, visual acuity and side effects over the course of the follow-up. RESULTS: A total of four patients were included in this report. Mean follow-up time was 31 months, and all patients showed decreased tumour volume and signs of fibrosis during follow-up. One patient remained stable in terms of visual acuity, two patients lost visual acuity and one patient improved and had a functional visual acuity at last follow-up. One patient developed radiation retinopathy with subsequent neovascular glaucoma that needed further management. All other patients did not show any signs of radiation induced side effects. CONCLUSION: We report on the outcome of robotic CyberKnife radiosurgery in the treatment of uveal metastasis. We believe that single session, outpatient treatment delivery that can be facilitated with CyberKnife radiosurgery offer some benefits for this particularly sick group of patients.

Robotic-assisted radiosurgery for the treatment of vasoproliferative tumours.

PURPOSE: Vasoproliferative tumours (VPT) are a rare but benign entity that can lead to severe visual acuity deterioration. There is no standard of care, and depending on the degree of clinical features, including tumour size and dissemination, visual acuity and subretinal fluid, treatment options include observation, cryotherapy and brachytherapy. Particularly in larger tumours, brachytherapy has advantages over other options, although higher radiation doses and the need for surgical application are disadvantages of this otherwise effective treatment option. CyberKnife radiosurgery might represent an alternative therapeutic option as no surgical intervention is needed and radiation doses are lower. METHODS: All patients diagnosed with vasoproliferative tumors who were treated with CyberKnife radiosurgery with a minimum follow-up time of 12 months were included in this case series. We recorded visual acuity, number of lesions, central retinal thickness with optical coherence tomography (OCT) and reflectivity using A-scan standardizes echography every three months. RESULTS: A total of four patients with a median age of 34 years (range: 24 - 51) who were observed over an average of 26.5 months (range: 17 - 49 months) matched our inclusion criteria. We appreciated stabilization or increase in visual acuity in all four patients and a regression in tumour thickness with subsequent increase in internal reflectivity as a marker of increasing fibrosis. CONCLUSION: We observed good visual and functional outcome following CyberKnife therapy for VPT. We believe that further studies should be pursued to evaluate CyberKnife therapy for the treatment of VPT not treatable with cryo- or lasertherapy.

Comparison of variables measured with a Scheimpflug device for evaluation of progression and detection of keratoconus.

Keratoconus is a progressive ectatic corneal disorder, which can result in severe visual impairment. The new ABCD keratoconus classification system allows differentiated description of the disease. Aim of the study was to evaluate the components of this novel staging system (ARC, PRC, thinnest pachymetry) as well as topometric indices, deviation of normality indices, and other parameters in terms of repeatability and reliability. 317 eyes with keratoconus were examined twice with a Scheimpflug device (Pentacam, Oculus). Bland Altman analysis and intraclass correlations were carried out to evaluate the parameters repeatability and reliability. Apart from IHA (ICC = 0.730), all parameters showed excellent reliability (ICC > 0.900). ARC, PRC, thinnest pachymetry, Kmax, CKI, KI, Rmin, and Progression Avg were the best repeatable parameters with relative repeatability values < 2.5%. Other parameters performing well in terms of repeatability were IHD, ISV, IVA, and final D (RR < 13%). Regression analysis revealed consistently high repeatability along all stages of keratoconus for PRC, thinnest pachymetry, and CKI. All parameters of the ABCD staging system showed excellent reliability and repeatability, PRC and thinnest pachymetry even at all stages of keratoconus and can consequently be reliably used in the determination of keratoconus progression.

Corneal wavefront aberrations and subjective quality of vision after small incision lenticule extraction.

PURPOSE: To analyse in depth the associations between objectively measured corneal higher-order aberrations (HOAs) and subjectively perceived visual quality after small incision lenticule extraction (SMILE) as quantified with the standardized and clinically validated quality of vision (QOV) questionnaire. METHODS: This cross-sectional study included patients after bilateral simultaneous SMILE for the treatment of myopia and/or myopic astigmatism with plano target refraction. Scheimpflug imaging (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was used to objectively quantify corneal HOAs. The standardized and validated QOV questionnaire was employed to gauge patients' subjectively perceived visual quality regarding frequency, severity and bothering effect of visual disturbances. RESULTS: A total of 394 eyes of 197 patients with a mean age of 32.4 ± 7.7 years and a mean postoperative follow-up of 24.3 ± 14.1 months were included. SMILE induced a statistically significant (p < 0.001) increase in spherical aberration (0.074 ± 0.131 µm), coma (0.142 ± 0.179 µm), trefoil (0.018 ± 0.067 µm) as well as in total HOAs (0.191 ± 0.176 µm). Surgically induced and postoperative levels of HOA showed no correlation with the three QOV scores representative of overall visual symptom frequency, severity and bothering effect (all R2 values ≤ 0.016). In addition, the associations between specific visual symptoms (e.g. starburst) and singular HOA terms (e.g. haloes) were very weak (all Rho values ≤ 0.164). CONCLUSIONS: Small incision lenticule extraction induced significant amounts of corneal HOAs that, however, showed no clear relationships to patient-reported QOV or specific long-term visual symptoms.

SMILE Versus Implantable Collamer Lens Implantation for High Myopia: A Matched Comparative Study.

PURPOSE: To compare the safety, efficacy, and patient-reported quality of vision of small incision lenticule extraction (SMILE) and implantable Collamer lens (ICL) implantation for the treatment of high myopia. METHODS: A database of 1,634 SMILE (Carl Zeiss Meditec AG, Jena, Germany) and 225 ICL implantation (STAAR Surgical, Monrovia, CA) procedures was screened for patients with a binocular preoperative manifest refraction spherical equivalent between -6.00 and -10.00 diopters (D) and plano target refraction. One-to-one matching was performed by preoperative manifest refraction spherical equivalent, age, and pupil size. All identified patients were then prospectively examined at their next regular postoperative follow-up visit and presented with the standardized and clinically validated Quality of Vision questionnaire to gauge patient-reported postoperative visual quality. RESULTS: A total of 80 eyes (40 patients) were eligible for 1:1 matching. Mean postoperative follow-up was 27.8 ± 14.3 months in the SMILE group and 26.6 ± 17.7 months in the ICL group (P = .44). Regarding the percentage of eyes within ±0.50 D of plano target, refractive predictability was better in eyes treated with ICL implantation (90%) than SMILE (72.5%) (P = .045). Mean UDVA was comparable (ICL: -0.09 ± 0.10 logMAR; SMILE: -0.06 ± 0.09 logMAR; P < .09), but the efficacy (1.28 vs 1.05; P < .001) and safety (1.31 ± 0.22 vs 1.10 ± 0.25; P < .001) indices were higher after ICL implantation. ICL implantation induced significantly fewer higher order aberrations (total higher order aberrations: SMILE 0.724 ± 0.174 µm vs ICL 0.436 ± 0.114 µm; P < .01). Regarding subjective quality of vision, patients who had ICL implantation were significantly less bothered by visual disturbances, which were mainly halos after ICL and starbursts and fluctuations of vision after SMILE (P < .05). CONCLUSIONS: In this refraction-matched comparative study, ICL implantation for high myopia yielded better refractive accuracy, better uncorrected distance visual acuity, fewer higher order aberrations, and better subjective quality of vision than SMILE. [J Refract Surg. 2020;36(3):150-159.].

Determinants of subjective patient-reported quality of vision after small-incision lenticule extraction.

PURPOSE: To characterize patient-reported long-term quality of vision (QoV) after small-incision lenticule extraction (SMILE), and to identify potential clinical parameters that might predispose to experiencing deteriorated visual quality. SETTING: University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany. DESIGN: Prospective cross-sectional study. METHODS: For the assessment and scoring of visual symptoms, the Quality of Vision questionnaire was employed, which constitutes a clinically validated, linear-scaled 30-item instrument providing a QoV score on three scales (symptom frequency, severity, and bothersome). Subgroup analyses were performed for patient subgroups stratified by baseline characteristics (eg, age) and treatment parameters (eg, surgical refractive correction) as well as refractive outcomes (eg, residual refraction) and visual outcomes (eg, uncorrected distance visual acuity [UDVA]). RESULTS: The study comprised 394 eyes of 197 patients (117 women [59.4%], 80 men [40.6%]) were included with a mean postoperative follow-up of 24.4 months ± 14.1 (SD). The QoV scores for symptom frequency, severity, and bothersome were 34.63 ± 13.69, 29.60 ± 12.38, and 24.56 ± 16.00, respectively. Patients with a preoperative binocular corrected distance visual acuity (CDVA) of 20/12.5 or better, patients who lost 1 or more lines of UDVA as compared with preoperative CDVA, patients older than the age of 40, and patients with inadvertent anisometropia more than 0.375 diopters reported worse QoV scores. CONCLUSION: The relationship between objective clinical parameters and patient-reported subjective QoV after SMILE seems complex. Defined prognostic factors that convey a higher risk for experiencing visual disturbances were identifiable and should be discussed with patients seeking SMILE treatment during preoperative counseling.

Ward rounds in internal medicine: Validation of an Entrustable Professional Activity (EPA) observation checklist.

Objectives: Ward rounds serve a crucial daily activity in hospitals. Building on the Entrustable Professional Activity "Conducting internal medicine ward rounds" consisting of ten competencies and 25 corresponding activities, this study aims at assessing content and external validity of an observation checklist for this EPA. Methods: A focus group aimed at content validation of the checklist. Five participants therefore evaluated it with respect to comprehensiveness and comprehensibility. To investigate external validity, 14 authentic ward rounds were video-taped and rated by two raters with the adapted observation checklist in terms of the appearance of certain activities in the videos. Results: After some adaptions, participants of the focus group agreed on a checklist consisting of nine competencies, 25 activities and 110 examples of observable behaviours supporting content validity. External validity was studied by using the observation checklist for ratings of ward round videos. The checklist was regarded as a valuable tool to structure observation. Along with the high frequencies of observed behaviour and interrater-reliability, external validity can be assumed. Conclusion: The first scientifically developed comprehensive observation checklist for the EPA conducting a ward round in internal medicine is presented. The checklist is a valuable tool for providing elaborated feedback in undergraduate and graduate medical education. Focussing on multi-institutional validation and the cut offs of the checklist to determine the levels of entrustment are recommended for future research.