Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials. METHODS: Four days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 106 cells were injected at three sites within the infarcted left ventricular (LV) wall. RESULTS: One month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits. CONCLUSIONS: The authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an "off-the-shelf" stem cell therapy for cardiac repair.

Concurrent Transcatheter Aortic Valve Replacement and Leadless Pacemaker Implantation in a Patient With Aortic Stenosis and Tachycardia-Bradycardia Syndrome.

We present a patient with symptomatic severe aortic stenosis and atrial fibrillation complicated by tachycardia-bradycardia syndrome, deemed too high-risk for surgical valve replacement and referred for transcatheter aortic valve replacement. We show that concurrent implantation of a leadless pacemaker system can be performed successfully with minimal additional risk to the patient, and also, that it can be used to rapidly pace the ventricles to assist in balloon valvuloplasty and prosthetic aortic valve deployment.

Nous présentons le cas d'un patient ayant une sténose aortique symptomatique grave et une fibrillation auriculaire compliquée par un syndrome tachycardie-bradycardie, jugé comme présentant un risque trop élevé pour être candidat à un remplacement valvulaire chirurgical, et orienté pour subir un remplacement valvulaire aortique par cathéter. Nous démontrons que l'implantation concomitante d'un système de stimulateur cardiaque sans fil peut être réalisée avec succès tout en entraînant un risque additionnel minime pour le patient, et que celui-ci peut être utilisé pour stimuler rapidement les ventricules afin de faciliter la valvuloplastie par ballonnet et le déploiement de la prothèse valvulaire aortique.

The role of intracoronary thrombolysis in selected patients presenting with ST-elevation myocardial infarction: a case series.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the cornerstone of management for ST-elevation myocardial infarction (STEMI). However, large intracoronary thrombus burden complicates up to 70% of STEMI cases. Adjunct therapies described to address intracoronary thrombus include manual and mechanical thrombectomy, use of distal protection device and intracoronary anti-thrombotic therapies. CASE SUMMARY: This series demonstrates the use of intracoronary thrombolysis in the setting of large coronary thrombus, bifurcation lesions with vessel size mismatch, diffuse thrombosis without underlying plaque rupture, and improving coronary flow to allow vessel wiring and proceeding to definitive revascularization. DISCUSSION: Larger intracoronary thrombus burden correlates with greater infarct size, distal embolization, and the associated no-reflow phenomena, and propagates stent thrombosis, with subsequent increase in mortality and major adverse cardiac events. Intracoronary thrombolysis may provide useful adjunct therapy in highly selected STEMI cases to reduce intracoronary thrombus and facilitate revascularization.

The Vancouver 3M (Multidisciplinary, Multimodality, But Minimalist) Clinical Pathway Facilitates Safe Next-Day Discharge Home at Low-, Medium-, and High-Volume Transfemoral Transcatheter Aortic Valve Replacement Centers: The 3M TAVR Study.

OBJECTIVES: The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway. BACKGROUND: Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines. METHODS: Patients were enrolled from 6 low-volume (<100 TAVR/year), 4 medium-volume, and 3 high-volume (>200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR. RESULTS: Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15). CONCLUSIONS: Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes.

Human Connexin40 Mutations Slow Conduction and Increase Propensity for Atrial Fibrillation.

BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS: Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene). Electrophysiology studies (EPS) were performed just prior to and 7 days after surgery. Left atria were assessed for connexin expression, mRNA levels, inflammation and fibrosis. Primary cardiomyocyte cultures were also transduced with the abovementioned vectors (n=6 per transgene) and monolayer conduction velocities (CV) and protein expression were assessed at 96hours. RESULTS: At day 7 EPS, P wave and induced atrial fibrillation (AF) durations were significantly longer in the mutant groups when compared to wtCx40 controls (p<0.05). There were no significant differences in inflammation, fibrosis, or heart to body weight ratios. Monolayer CV's were reduced in the A96S group compared to the wtCx40 group. While similar to wtCx40 controls, P88S velocities were reduced compared to eGFP controls. G38D monolayers possessed spontaneous fibrillatory activity and could not be paced. Immunofluorescence revealed that P88S and G38D reduced native connexin43 myocyte coupling while A96S appeared to co-localise with connexin43 in gap junctions. Connexin43 mRNA levels were similar between groups. CONCLUSIONS: The A96S, G38D, and P88S Cx40 mutations slow conduction and increased the propensity for inducible AF.

Retrieval of embolized left atrial appendage devices.

Percutaneous left atrial appendage (LAA) closure is gaining interest as an alternative option for prevention of strokes in patients with Atrial Fibrillation (AF), especially for those with contraindications to anticoagulation. Complications from these procedures are well described in the medical literature. LAA closures may lead to pericardial effusion, device-associated thrombus, and device embolization. Understanding the reasons for embolization, strategies to avoid embolization, and the techniques for retrieval of LAA devices (ACP/AMULET and WATCHMAN) should be appreciated by endovascular implanters. We describe two cases of LAA device embolization that were both successfully retrieved percutaneously and other percutaneous techniques to safely retrieve embolized LAA devices. © 2016 Wiley Periodicals, Inc.

The prognostic importance of the diastolic pulmonary gradient, transpulmonary gradient, and pulmonary vascular resistance in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the association between markers of precapillary pulmonary hypertension (PH) and survival in transcatheter aortic valve replacement (TAVR). BACKGROUND: The importance of precapillary PH has been sparsely investigated in patients undergoing TAVR. It may prove an important risk factor for poor outcomes. METHODS: We identified patients at our institution undergoing TAVR with a baseline right heart catheterization (RHC) demonstrating PH. We evaluated the association between markers of precapillary PH and survival including the diastolic pulmonary gradient (DPG), transpulmonary gradient (TPG), and pulmonary vascular resistance (PVR). A multivariable analysis was performed using Cox Proportional Hazards Models, adjusting for age, gender, body mass index, and pulmonary artery systolic pressure (PASP) on echocardiography. RESULTS: We identified 133 patients with PH on RHC. Of these 111 had low DPG and 22 had high DPG. All 3 markers of precapillary PH were associated with worse survival post TAVR, with OR of 2.1 (95% CI 1.1-3.9, P = 0.02), 3.4 (95% CI 1.8-6.4, P < 0.001) and 2.5 (95% CI 1.4-4.5, P = 0.003) for high DPG, TPG, and PVR, respectively. On multivariable analysis, both TPG and PVR remained predictors of worse survival, with OR of 3.4 (95% CI 1.7-6.9, P = 0.001) and 2.5 (95% CI 1.4-4.5, P = 0.003). Echocardiographic PASP and DPG were not predictive of survival. CONCLUSIONS: In patients undergoing TAVR, parameters of precapillary PH are associated with lower survival, and provide incremental prognostication over echocardiographic PASP. RHC should continue to play an important role in risk stratification prior to TAVR. © 2017 Wiley Periodicals, Inc.

Early Canadian Multicenter Experience With WATCHMAN for Percutaneous Left Atrial Appendage Closure.

BACKGROUND: There are limited data with WATCHMAN (Boston Scientific Corporation, Natick, MA, USA) for left atrial appendage (LAA) closure in patients with nonvalvular atrial fibrillation (AF) and contraindications to anticoagulation. The purpose of this study was to evaluate the safety and efficacy of WATCHMAN in our early Canadian experience. METHODS: We report our pooled consecutive series of patients who underwent WATCHMAN implantation at four major Canadian centers. Indications for LAA closure were CHADS2 ≥ 1 or CHA2 DS2 -VASc ≥ 2, and contraindication/intolerance to or failure on anticoagulation. Follow-up imaging was typically performed 1-6 months postprocedure. RESULTS: One hundred and six patients underwent LAA closure with WATCHMAN from May 2013 to October 2015. The mean age was 74.8 ± 7.7, mean CHADS2 score was 2.8 ± 1.2, CHA2 DS2 -VASc score was 4.3 ± 1.5, and HASBLED score was 3.2 ± 1.2. Permanent AF was present in 67.9% and paroxysmal AF in 32.1%. Indications for LAA closure were prior bleeding 89.6% (87 major bleeding and 8 minor bleeding), 9.4% were deemed high risk for bleeding, and 0.9% with recurrent strokes on warfarin. Procedural success was 97.2% (103 of 106), with one device embolization (snared percutaneously), one implant failure due to inadequate LAA depth, and one cardiac perforation requiring surgical repair before WATCHMAN implantation. The composite major safety event-rate was 1.9% (1 death and 1 device embolization). Mean hospital stay was 1.8 ± 4.7 days. Antithrombotic therapy postimplant included dual antiplatelet therapy in 76 of 103 (73.8%). Mean follow-up was 210 ± 182 days; there were two transient ischemic attacks, with estimated 66% reduction in thromboembolic events relative to CHADS2 predicted risk. CONCLUSION: In our early Canadian experience, WATCHMAN for LAA closure in patients contraindicated to anticoagulation appeared safe and effective.

Clinical characteristics, angiographic findings, and one-year outcome of 101 consecutive stent thrombosis cases in British Columbia.

BACKGROUND: Stent thrombosis (ST) is rare, but is associated with significant morbidity and mortality. METHODS: We analyzed data from the British Columbia (BC) Registry from April 2011-January 2012. RESULTS: 101 ST cases were reported and verified. Based on timing, ST was considered early (≤30days) in 35.6%, late (>30days-1year) in 17.8% and very late (>1year) in 46.5%. The majority (68.5%) presented with STEMI, and the remaining with non-STEMI (31.5%). Most vessels were functionally occluded (TIM1 flow grade ≤1 in 67.1%). Thrombus burden was high (TIMI thrombus grade ≥4 in 77.2%). Aspiration thrombectomy was performed in 41% of cases. New stents were implanted in 62.4% cases. Intra-coronary imaging was low (11%). At the original stent implantation, STEMI was the clinical presentation in 39.6%, the lesion was complex in 62.1%, and thrombus was visualized in 23.0%. Prognosis after ST was unfavorable with high mortality (11.9% at 30days and 16.8% at one year), and further revascularization (5.0% repeat PCI and 6.9% coronary artery bypass graft surgery). Early ST was associated with worse clinical outcome compared to late/very late ST: 30-day mortality at 22.2% versus 6.2% (p=0.02), and 1-year mortality at 27.8% versus 10.8% (p=0.05). CONCLUSIONS: In this prospective registry from BC, all ST presented with myocardial infarction, and the majority was treated with emergency PCI. Additional stents were commonly implanted with infrequent use of intracoronary imaging. Mortality rate was higher for early ST in comparison with late/very late ST. A comprehensive approach should be developed to treat this difficult complication.

Left Atrial Appendage Closure for Atrial Fibrillation Is Safe and Effective After Intracranial or Intraocular Hemorrhage.

BACKGROUND: Atrial fibrillation (AF) affects 1%-2% of the general population and 13% of individuals older than 80 years of age. Anticoagulation has been the mainstay therapy to reduce stroke risk. Patients with previous intracranial hemorrhage (ICH) or intraocular hemorrhage (IOH) are at increased risk of recurrence if anticoagulation is continued or initiated. Left atrial appendage (LAA) closure may obviate the need for long-term anticoagulation in these patients. METHODS: We report our consecutive series of patients with nonvalvular AF with previous ICH or IOH who underwent LAA closure with the AMPLATZER Cardiac Plug (ACP; St Jude Medical, St Paul, MN), AMPLATZER Amulet, or WATCHMAN (Boston Scientific, Natick, MA) device. Demographics, clinical status, procedural outcomes, and complications were collected at baseline, during the procedure, at 3 months, at 1 year, and annually thereafter. RESULTS: Twenty-six patients with previous ICH (n = 24) or IOH (n = 2) underwent LAA closure (9 with the ACP, 3 with the Amulet, and 7 with the WATCHMAN). The mean age was 76 ± 7 years, and 61.5% were men with a mean CHADS2 (Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) score of 3.2 ± 1.4 and CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age [≥ 75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female] score) of 4.9 ± 1.7. No procedure-related complications occurred. Mean follow-up was 11.9 ± 13.3 months. One patient died at 13 months (this death was not related to the procedure), and 1 patient had a transient ischemic attack at 20.6 months after the procedure. No ischemic stroke, haemorrhagic stroke, or bleeding problems occurred during follow-up. CONCLUSIONS: In our consecutive series, LAA closure was found to be safe and effective in patients with AF and a history of ICH or IOH.

Comparing Measurements of CT Angiography, TEE, and Fluoroscopy of the Left Atrial Appendage for Percutaneous Closure.

BACKGROUND: Left atrial appendage (LAA) closure requires accurate preprocedural measurements, and trans-esophageal echocardiography (TEE), cardiac computed tomography angiography (CCTA) and fluoroscopy can be utilized. However, correlations between these measurements remain inadequately assessed. METHODS: Patients who underwent LAA closure at Vancouver General Hospital who had baseline LAA measurements by CCTA, TEE, and fluoroscopy were included in this analysis. CCTAs were performed with prospective-ECG-gating with Toshiba 320-detector or Siemens second generation 128-slice dual-source scanners, and images interpreted with VitreaWorkstation.™ LAA maximal dimensions were obtained for all patients at: (1) Amplatzer Cardiac Plug (ACP)/Amulet landing zone 10 mm within orifice, (2) WATCHMAN ostium, and (3) WATCHMAN depth measurements. Correlations and agreements were compared. RESULTS: We report 50 consecutive patients who underwent LAA closure (8 ACP, 10 Amulet, 32 WATCHMAN). Average age was 75.2 ± 8.7 years, mean CHADS2 score 3.0 ± 1.3, and CHA2 DS2 -VASc 4.7 ± 1.5. Procedural device implantation success was 100%. For ACP landing zone, mean maximal measurements were 24.1 ± 4.7 mm with CCTA, 22.3 ± 4.9 mm TEE, and 19.9 ± 5.6 mm fluoroscopy (P < 0.001); R value 0.81 fluoroscopy/CTA, 0.67 fluoroscopy/TEE, and 0.80 CTA/TEE. For WATCHMAN ostium, mean maximal measurements were 25.8 ± 4.7 mm CCTA (P < 0.001 vs. fluoroscopy, P = 0.16 vs. TEE), 25.1 ± 4.4 mm TEE (P = 0.016 vs. fluoroscopy), and 23.8 ± 4.9 mm fluoroscopy; R value 0.71 fluoroscopy/CTA, 0.65 fluoroscopy/TEE, and 0.74 CTA/TEE. Depth measurements were 34.3 ± 5.7 mm with CCTA, 31.1 ± 6.5 mm TEE, and 27.8 ± 7.1 mm fluoroscopy (all P < 0.01); and correlations with R value 0.28 fluoroscopy/CTA, 0.22 fluoroscopy/TEE, and 0.56 CTA/TEE. CONCLUSIONS: All 3 imaging modalities correlated with ACP landing zone and WATCHMAN ostium measurements, with CCTA providing the largest measurements, followed by TEE and fluoroscopy.

Cardiac CT angiography for device surveillance after endovascular left atrial appendage closure.

AIMS: Left atrial appendage (LAA) device imaging after endovascular closure is important to assess for device thrombus, residual leak, positioning, surrounding structures, and pericardial effusion. Cardiac CT angiography (CCTA) is well suited to assess these non-invasively. METHODS AND RESULTS: We report our consecutive series of non-valvular atrial fibrillation patients who underwent CCTA post-LAA closure with Amplatzer Cardiac Plug (ACP), Amulet (second generation ACP), or WATCHMAN devices. Patients underwent CCTA typically 1-6 months post-implantation. Prospective cardiac-gated CCTA was performed with Toshiba 320-detector or Siemens 2nd generation 128-slice dual-source scanners, and images interpreted with VitreaWorkstation™. GFR <30 mL/min/1.73 m(2) was an exclusion. We assessed for device thrombus, residual LAA leak, device embolization, position, pericardial effusion, optimal implantation, and device lobe dimensions. Forty-five patients underwent CCTA at median 97 days post-LAA closure (18 ACP, 9 Amulet, 18 WATCHMAN). Average age was 75.5 ± 8.9 years, mean CHADS2 score 3.1 ± 1.3, and CHADS-VASc score 4.9 ± 1.6. All had contraindications to oral anticoagulation. Post-procedure, 41 (91.1%) were discharged on DAPT. There was one device embolization (ACP, successfully retrieved percutaneously) and one thrombus (WATCHMAN, resolved with 3 months of warfarin). There were two pericardial effusions, both pre-existing and not requiring intervention. Residual leak (patency) was seen in 28/44 (63.6%), and the mechanisms of leak were readily identified by CCTA (off-axis device, gaps at orifice, or fabric leak). Mean follow-up was 1.2 ± 1.1year, with no death, stroke, or systemic embolism. CONCLUSION: CCTA appears to be a feasible alternative to transoesophageal echocardiography for post-LAA device surveillance to evaluate for device thrombus, residual leak, embolization, position, and pericardial effusion.

Changes in Left Atrial Appendage Dimensions Following Volume Loading During Percutaneous Left Atrial Appendage Closure.

OBJECTIVES: This study sought to determine whether volume loading alters the left atrial appendage (LAA) dimensions in patients undergoing percutaneous LAA closure. BACKGROUND: Percutaneous LAA closure is increasingly performed in patients with atrial fibrillation and contraindications to anticoagulation, to lower their stroke and systemic embolism risk. The safety and efficacy of LAA closure relies on accurate device sizing, which necessitates accurate measurement of LAA dimensions. LAA size may change with volume status, and because patients are fasting for these procedures, intraprocedural measurements may not be representative of true LAA size. METHODS: Thirty-one consecutive patients undergoing percutaneous LAA closure who received volume loading during the procedure were included in this study. After an overnight fast and induction of general anesthesia, patients had their LAA dimensions (orifice and depth) measured by transesophageal echocardiography before and after 500 to 1,000 ml of intravenous normal saline, aiming for a left atrial pressure >12 mm Hg. RESULTS: Successful implantation of LAA closure device was achieved in all patients. The average orifice size of the LAA at baseline was 20.5 mm at 90°, and 22.5 mm at 135°. Following volume loading, the average orifice size of the LAA increased to 22.5 mm at 90°, and 23.5 mm at 135°. The average increase in orifice was 1.9 mm (p < 0.0001). The depth of the LAA also increased by an average of 2.5 mm after volume loading (p < 0.0001). CONCLUSIONS: Intraprocedural volume loading with saline increased the LAA orifice and depth dimensions during LAA closure. Operators should consider optimizing the left atrial pressure with volume loading before final device sizing.

Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia.

BACKGROUND: Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. METHODS AND RESULTS: Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). CONCLUSIONS: Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.

Metastases in the ophthalmic region in Denmark 1969-98. A histopathological study.

PURPOSE: To evaluate the patterns of origin and anatomical localization of histologically verified metastases in the ophthalmic region in Denmark during 1969-98, and to compare the findings with those of a similar study for the period 1944-68. METHODS: All metastatic lesions presented at the Eye Pathology Institute, University of Copenhagen during the period 1968-98 were investigated. RESULTS: Metastases were found in 81 specimens from the eye and eye region in 76 patients (32 men, 44 women). Five patients had bilateral involvement. The most frequent site of involvement was the uvea (63%), followed by the orbit (26%) and the eyelids (10%). Breast cancer accounted for the most frequent primary tumour (38%), followed by lung cancer (24%) and skin melanoma (14%). CONCLUSION: The pattern of anatomical location of metastases in the ocular region has not changed since 1944. The incidence of metastases has fallen significantly throughout the period.