Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride in Non-invasive Axillary Staging in Breast Cancer: Are we Missing a Chance?

BACKGROUND/AIM: In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). PATIENTS AND METHODS: A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. RESULTS: After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. CONCLUSION: The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.

FIL SSF intraocular lens opacification after gas tamponade: A case series.

PURPOSE: To report three cases of postoperative opacification of sutureless scleral-fixed hydrophilic intraocular lens (FIL SSF IOL, Soleko, Italy) after gas tamponade. Two cases occurred after pars plana vitrectomy and one case after Descemet membrane endothelial keratoplasty. CASE REPORT: Two diabetic patients underwent a FIL SSF IOL implantation after posterior capsular rupture during cataract surgery. Rhegmatogenous retinal detachment (RRD) was observed in one patient during the initial surgery. A second patient developed a RRD five months after surgery. Both RRDs were treated with pars plana vitrectomy and perfluoroethane (C2F6) gas tamponade. A few days after the surgery, C2F6 was observed in the anterior chamber of both patients. Two months after gas tamponade, opacification of the anterior surface of the IOL was observed. The third patient was a 74-year-old woman, who underwent a combined Descemet membrane endothelial keratoplasty (DMEK) and FIL SSF IOL implantation. Two rebubblings with sulfur hexafluoride (SF6) retreatments were required due to corneal graft detachment. One month later, an opacification of the anterior surface of the IOL was observed. Explantation with implantation of iris-claw IOL was decided, which resulted in an improvement of BVCA. Analysis of the IOL showed a positive Von Kossa staining, indicating calcification of the IOL. We performed a review of all the cases of FIL SSF IOL implantation in our centers. The overall rate of FIL SSF IOL opacification was 2.1% (3/140). Amongst patients treated with gas tamponade, the rate of opacification was 27.3% (3/11). Although FIL SSF IOL implantation appears to be an effective option for the treatment of aphakia, caution should be exercised regarding the risk of opacification following gas tamponade, especially since these patients are at risk of retinal detachment.

SF 6 COMPARED WITH C 2 F 6 FOR INFERIOR RHEGMATOGENOUS RETINAL REPAIR : The Manchester Pseudophakic Retinal Detachment Study.

PURPOSE: To compare SF 6 relative with C 2 F 6 in the anatomical and functional outcomes following pars plana vitrectomy for uncomplicated primary pseudophakic rhegmatogenous retinal detachment with inferior causative breaks. METHODS: This is a retrospective, comparative study on eyes with pseudophakic rhegmatogenous retinal detachment with inferior causative breaks that had small-gauge pars plana vitrectomy repair using SF 6 and C 2 F 6 tamponade between 2011 and 2020 at a tertiary centre in the United Kingdom. Primary outcome was single surgery anatomical success, and the secondary outcome was best-corrected visual acuity. Propensity score matching, using preoperative findings as covariates to account for relevant confounders, was performed. RESULTS: From 162 pseudophakic rhegmatogenous retinal detachment eyes with inferior causative breaks, the median (interquartile range) follow-up was 82 (52-182) days. The single surgery anatomical success was 156 (96.3%) overall: 47 of 47 (100.0%) and 109 of 115 (94.8%) in the SF 6 and C 2 F 6 groups, respectively ( P = 0.182). Relative to the SF 6 group, the C 2 F 6 group had a higher mean number of tears (SF 6 : 3.1[2.0], C 2 F 6 : 4.5[2.7], P = 0.002) and greater retinal detachment extent (SF 6 : 5.3[2.9], C 2 F 6 : 6.2[2.6] clock hours, P = 0.025). Following propensity score matching analysis, 80 eyes were matched with 40 in each group to homogenize preoperative factors. No significant difference was found in single surgery anatomical success and best-corrected visual acuity between the groups following propensity score matching. CONCLUSION: Primary pars plana vitrectomy with gas tamponade leads to a high single surgery anatomical success rate in uncomplicated pseudophakic rhegmatogenous retinal detachment with inferior causative breaks with no additional benefit associated with long-acting tamponade when comparing C 2 F 6 with SF 6 .

RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.

PURPOSE: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. METHODS: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). RESULTS: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. CONCLUSION: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

Pneumatic retinopexy as a treatment for rhegmatogenous retinal detachment in pediatric patients meeting PIVOT criteria.

OBJECTIVE: To report the results of pneumatic retinopexy (PnR) as the initial treatment in pediatric patients with rhegmatogenous retinal detachment (RRD) fulfilling The Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) criteria. DESIGN: A retrospective multicentre study. PARTICIPANTS: Pediatric patients who underwent outpatient PnR as the initial treatment for RRD from January 2006 to July 2019 who met PIVOT criteria. METHODS: Patients underwent anterior chamber paracentesis followed by intravitreal injection of sulfur hexafluoride (SF6) gas. Either laser retinopexy was performed following retinal reattachment or cryopexy was performed at the time of the initial procedure. RESULTS: A total of 20 eyes of 20 consecutive patients met inclusion criteria and were included in this study. Mean (± standard deviation [SD]) follow-up time was 42.2 ± 38.0 months. Mean patient age was 14.4 years (range, 9-18). There were 17 males and 3 females. The mean (± SD) logMar visual acuity improved from 0.73 ± 0.82 (Snellen equivalent approximately 20/100) to 0.37 ± 0.46 (Snellen equivalent approximately 20/50; p = 0.02) at 3 months and to 0.40 ± 0.54 (Snellen equivalent approximately 20/50; p = 0.05) at last follow-up. Primary reattachment rate was 85% (17/20) at 3 months and 75% (15/20) at last follow-up visit. CONCLUSIONS: PnR may be an effective treatment option for RRD in pediatric patients meeting PIVOT criteria.

Comparison of lymphatic contrast-enhanced ultrasound and intravenous contrast-enhanced ultrasound in the preoperative diagnosis of axillary sentinel lymph node metastasis in patients with breast cancer.

OBJECTIVES: This study aimed to compare diagnostic efficiency for axillary sentinel lymph node (SLN) metastasis between lymphatic contrast-enhanced ultrasound (LCEUS) and intravenous contrast-enhanced ultrasound (ICEUS) in patients with breast cancer. We also examined whether adding ICEUS to LCEUS could improve the diagnostic accuracy of LCEUS. METHODS: Sixty-nine patients with breast cancer were recruited preoperatively. All patients underwent LCEUS followed by ICEUS, and the enhancement pattern of one SLN was analysed for each patient. The targeted SLN was marked with wire and excised during surgery. The imaging diagnosis was compared with the histopathological result. Diagnostic efficiency was compared among LCEUS, ICEUS, and the combination of LCEUS and ICEUS. RESULTS: The sensitivity values for LCEUS, ICEUS, and the combination of LCEUS and ICEUS were 86.2%, 82.6% and 93.1%, respectively. Specificity values for the three methods were 95.0%, 92.5% and 87.5%, respectively. Accuracy values for the three methods were 91.3%, 88.4% and 89.9%, respectively. The area under the receiver operating characteristic (ROC) curve for LCEUS was 0.906, and there was no significant difference among LCEUS, ICEUS, and the combination of LCEUS and ICEUS (p = 0.752). CONCLUSIONS: LCEUS may represent an accurate method for predicting SLN metastasis preoperatively. Our findings suggest that adding ICEUS to LCEUS for SLN evaluation in patients with breast cancer is unnecessary. ADVANCES IN KNOWLEDGE: This is the first study in which both LCEUS and ICEUS were performed for the same lymph node and the first to compare the diagnostic efficiency of LCEUS, ICEUS, and the combination of LCEUS + ICEUS.

LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments. METHOD: A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair. RESULTS: One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481). CONCLUSION: We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

MACULAR HOLE ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION: Pathogenesis and Surgical Outcomes.

PURPOSE: To ascertain the pathogenesis of macular hole (MH) associated with age-related macular degeneration (AMD) and its surgical outcomes. METHODS: Patients with full-thickness MH associated with AMD (higher grades than intermediate) were enrolled. The mechanism of MH formation and closure rate after vitrectomy (surgical outcome) were determined using optical coherence tomography imaging. RESULTS: The mechanism of MH formation (35 eyes) associated with AMD was classified into four types: vitreomacular traction (42.9%), gradual retinal thinning caused by subretinal drusen or pigment epithelial detachment (22.9%), massive subretinal hemorrhage (20.0%), and combined (14.3%). In the 41 eyes that underwent vitrectomy, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.82 (0.10-2.30) preoperative to 0.69 (0.10-2.30) postoperative (P = 0.001). Successful closure of the MH was achieved in 33 eyes (80.5%) after vitrectomy. No significant association was observed between the closure rate of MH after vitrectomy and mechanism of MH formation (P = 0.083). CONCLUSION: The mechanism of MH formation associated with AMD was classified into four types and was not related to its surgical outcome. Considering visual improvement and surgical outcome after vitrectomy in our study, active surgical treatment can be considered for MH associated with AMD.

Ultrasound-targeted microbubble destruction promotes myocardial angiogenesis and functional improvements in rat model of diabetic cardiomyopathy.

BACKGROUND: Microvascular insufficiency plays an important role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. This study sought to verify the preclinical performance of SonoVue microbubbles (MB) combined ultrasound (US) treatment on myocardial angiogenesis in the rat model of DCM and investigate the optimal ultrasonic parameters. METHODS: The male Sprague-Dawley (SD) rats were induced DCM by streptozotocin through intraperitoneal injecting and fed with high-fat diet. After the DCM model was established, the rats were divided into the normal group, DCM model group, and US + MB group, while the US + MB group was divided into four subsets according to different pulse lengths (PL) (8 cycles;18 cycle;26 cycle; 36 cycle). After all interventions, all rats underwent conventional echocardiography to examine the cardiac function. The rats were sacrificed and myocardial tissue was examined by histology and morphometry evaluations to detect the myocardial protective effect of SonoVue MBs using US techniques. RESULTS: From morphologic observation and echocardiography, the DCM rats had a series of structural abnormalities of cardiac myocardium compared to the normal rats. The US-MB groups exerted cardioprotective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significant therapeutic effects on the cardiac functions in DCM rats. CONCLUSION: This strategy using SonoVue MB and US can improve the efficacy of angiogenesis, even reverse the progress of cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.

The Cologne rebubbling study: a reappraisal of 624 rebubblings after Descemet membrane endothelial keratoplasty.

BACKGROUND/AIMS: To analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye. METHODS: In this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK. RESULTS: Mean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 µm. Mean axial diameter was 382.53±282.02 µm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 µm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000). CONCLUSIONS: The overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.

HUMAN AMNIOTIC MEMBRANE TO TREAT MACULAR HOLES THAT FAILED TO CLOSE, SULFUR HEXAFLUORIDE ENDOTAMPONADE VERSUS AIR ENDOTAMPONADE: A Prospective Comparative Study.

BACKGROUND/PURPOSE: To determinate the efficacy of the human amniotic membrane plugs with sulfur hexafluoride versus human amniotic membrane plug with air as endotamponade to treat macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Multimodal imaging was focused to evaluate preoperative features and postoperative changes. METHODS: Prospective interventional comparative study. Twenty eyes of 20 patients affected with macular hole that failed to close were divided into 2 groups: 10 eyes received an amniotic membrane plug with 20% sulfur hexafluoride tamponade and 10 eyes received an amniotic membrane plug with air tamponade. All eyes were studied using multimodal advanced diagnostic tools, such as spectral-domain optical coherence tomography, optical coherence tomography angiography, microperimetry, and adaptive optics to investigate the postoperative results. RESULTS: In both groups, all macular holes were found successfully closed after 12 months. Mean preoperative best-corrected visual acuity was 20/400 in the SF6 group and 20/250 in air group. Final mean best-corrected visual acuity was 20/63 in both groups. The superficial capillary plexus, studied using optical coherence tomography angiography, showed a statistically significant difference between the treated and the fellow eyes. Adaptive optics images revealed the presence of a photoreceptor cell mosaic in the area of the amniotic membrane plug. CONCLUSION: The human amniotic membrane combined with air endotamponade demonstrated its effectiveness to seal macular holes that failed to close after vitrectomy plus internal limiting membrane peeling. Advanced multimodal diagnostic imaging helped us to better understand the modifications associated with the use of the amniotic membrane in these cases.

Transcholecystic Contrast-Enhanced Ultrasound-Guided Percutaneous Transhepatic Biliary Drainage for Central Bile Duct Protection During Thermal Tumor Ablation.

Intraductal cooling via a percutaneous transhepatic biliary drainage tube holds great promise in facilitating thermal ablation of liver tumors adjacent to the central bile ducts. However, the difficulties and complications associated with puncturing nondilated bile ducts are greater than those associated with puncturing dilated bile ducts. As reported here, percutaneous transcholecystic contrast-enhanced ultrasound was performed in 7 patients to visualize the nondilated bile ducts and guide percutaneous transhepatic biliary drainage, thus facilitating the intraductal cooling-assisted thermal ablation process. The procedures were technically successful in all 7 patients, and no major complications were recorded during the follow-up period.

Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane for the Diagnosis of Hepatocellular Carcinoma in Individuals with High Risk.

Background Perfluorobutane (PFB) and sulfur hexafluoride (SHF) have different physiologic characteristics, but it is unclear whether hepatocellular carcinomas (HCCs) show similar wash-in and washout patterns to both contrast agents at US. Purpose To investigate Contrast-Enhanced US Liver Imaging Reporting and Data System (LI-RADS) version 2017 HCC categorization by comparing PFB-enhanced US and SHF-enhanced US in participants at high risk for HCC. Materials and Methods In this prospective study conducted from February to August 2019, participants at high risk for HCC with treatment-naive hepatic observations (≥1 cm) categorized as LR-3, LR-4, LR-5, or LR-M (intermediate probability of HCC, probable HCC, definitely HCC, and probably malignant but not HCC specific, respectively) on cross-sectional images were screened. They underwent same-day PFB-enhanced US and SHF-enhanced US. Arterial phase hyperenhancement (APHE), washout time and degree, and echogenicity in the Kupffer phase (PFB-enhanced US) were evaluated and categorized by the operator using CEUS LI-RADS, who referred to the radiologist who performed the contrast-enhanced US, and by a reviewer. Diagnostic performance was analyzed using the McNemar test. Results Fifty-nine participants were evaluated (43 with HCC, 10 with non-HCC malignancies, six with benign findings). Nonrim APHE was identically observed in 95% (41 of 43, operator) or 88% (38 of 43, reviewer) of HCCs with both contrast agents. Among 43 HCCs, late (≥60 seconds) and mild washout were more frequent with PFB-enhanced US (34 with operator, 33 with reviewer) than with SHF-enhanced US (24 with operator, 26 with reviewer) (P = .04 or P = .12). The washout time for HCCs was later at PFB-enhanced US (median, 101 seconds ± 11) than at SHF-enhanced US (median, 84 seconds ± 5; P = .04). Sensitivity (34 of 43; 79%; 95% confidence interval [CI]: 64%, 90%) was higher with PFB-enhanced US than with SHF-enhanced US (23 of 43; 54%; 95% CI: 38%, 67%; P = .01). Specificity was 100% (95% CI: 79%, 100%) with both. Hypoenhancement in the Kupffer phase was more common in malignant (49 of 53 [92%] for both operator and reviewer) than in benign (two of six [33%] for operator, one of six [16%] for reviewer) lesions. Conclusion On the basis of the Contrast-Enhanced US Liver Imaging Reporting and Data System version 2017 algorithm, noninvasive US diagnosis of hepatocellular carcinoma by using perfluorobutane-enhanced US had higher diagnostic performance than sulfur hexafluoride-enhanced US, without loss of specificity. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kim and Jang in this issue.

Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound.

PURPOSE: Carotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. METHODS: The presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. RESULTS: Increased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. CONCLUSION: Increased carotid IPN is independently correlated with aggravated cerebral WMLs.

Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy.

BACKGROUND: Retinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery to restore normal anatomy and to stabilize or improve vision. PVR usually occurs in association with recurrent RD (that is, after initial retinal re-attachment surgery), but occasionally may be associated with primary RD. Either way, for both circumstances a tamponade agent (gas or silicone oil) is needed during surgery to reduce the rate of postoperative recurrent RD. OBJECTIVES: The objective of this review was to assess the relative safety and effectiveness of various tamponade agents used with surgery for RD complicated by PVR. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (the Cochrane Library 2019, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2019), Embase (January 1980 to January 2019), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2019), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 January 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) on participants undergoing surgery for RD associated with PVR that compared various tamponade agents. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results independently. We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified four RCTs (601 participants) that provided data for the primary and secondary outcomes. Three RCTs provided data on visual acuity, two reported on macular attachment, one on retinal reattachment and another two on adverse events such as RD, worsening visual acuity and intraocular pressure. Study Characteristics Participants' characteristics varied across studies and across intervention groups, with an age range between 21 to 89 years, and were predominantly men. The Silicone Study was conducted in the USA and consisted of two RCTs: (silicone oil versus sulfur hexafluoride (SF6) gas tamponades; 151 participants) and (silicone oil versus perfluropropane (C3F8) gas tamponades; 271 participants). The third RCT compared heavy silicone oil (a mixture of perfluorohexyloctane (F6H8) and silicone oil) with standard silicone oil (either 1000 centistokes or 5000 centistokes; 94 participants). The fourth RCT compared 1000 centistokes with 5000 centistokes silicone oil in 85 participants. We assessed most RCTs at low or unclear risk of bias for most 'Risk of bias' domains. Findings Although SF6 gas was reported to be associated with worse anatomic and visual outcomes than was silicone oil at one year (quantitative data not reported), at two years, silicone oil compared to SF6 gas showed no evidence of a difference in visual acuity (33% versus 51%; risk ratio (RR) 1.57; 95% confidence interval (CI) 0.93 to 2.66; 1 RCT, 87 participants; low-certainty evidence). At one year, another RCT comparing silicone oil and C3F8 gas found no evidence of a difference in visual acuity between the two groups (41% versus 39%; RR 0.97; 95% CI 0.73 to 1.31; 1 RCT, 264 participants; low-certainty evidence). In a third RCT, participants treated with standard silicone oil compared to those receiving heavy silicone oil also showed no evidence of a difference in the change in visual acuity at one year, measured on logMAR scale ( mean difference -0.03 logMAR; 95% CI -0.35 to 0.29; 1 RCT; 93 participants; low-certainty evidence). The fourth RCT with 5000-centistoke and 1000-centistoke comparisons did not report data on visual acuity. For macular attachment, participants treated with silicone oil may probably experience more favorable outcomes than did participants who received SF6 at both one year (quantitative data not reported) and two years (58% versus 79%; RR 1.37; 95% CI 1.01 to 1.86; 1 RCT; 87 participants; low-certainty evidence). In another RCT, silicone oil compared to C3F8 at one year found no evidence of difference in macular attachment (RR 1.00; 95% CI 0.86 to 1.15; 1 RCT, 264 participants; low-certainty evidence). One RCT that compared 5000 centistokes to 1000 centistoke reported that retinal reattachment was successful in 67 participants (78.8%) with first surgery and 79 participants (92.9%) with the second surgery, and no evidence of between-group difference (1 RCT; 85 participants; low-certainty evidence). The fourth RCT that compared standard silicone oil with heavy silicone oil did not report on macular attachment. Adverse events In one RCT (86 participants), those receiving standard 1000 centistoke silicone oil compared with those of the 5000 centistoke silicone oil showed no evidence of a difference in intraocular pressure elevation at 18 months (24% versus 22%; RR 0.90; 95% CI 0.41 to 1.94; low-certainty evidence), visually significant cataract (49% versus 64%; RR 1.30; 95% CI 0.89 to 1.89; low-certainty evidence), and incidence of retina detachment after the removal of silicone oil (RR 0.36 95% CI 0.08 to 1.67; low-certainty evidence). Another RCT that compared standard silicone oil with heavy silicone oil suggests no difference in retinal detachment at one year (25% versus 22%; RR 0.89; 95% CI 0.54 to 1.48; 1 RCT; 186 participants; low-certainty evidence). Retinal detachment was not reported in the RCTs that compared silicone oil versus SF6 and silicone oil versus to C3F8. AUTHORS' CONCLUSIONS: There do not appear to be any major differences in outcomes between C3F8 and silicone oil. Silicone oil may be better than SF6 for macular attachment and other short-term outcomes. The choice of a tamponade agent should be individualized for each patient. The use of either C3F8 or standard silicone oil appears reasonable for most patients with RD associated with PVR. Heavy silicone oil, which is not available for routine clinical use in the USA, may not demonstrate evidence of superiority over standard silicone oil.

Descemet Membrane Detachment After Penetrating Keratoplasty for Keratoconus.

PURPOSE: To describe the risk factors, management, and outcome of delayed Descemet membrane (DM) detachment after penetrating keratoplasty (PK) for keratoconus. METHODS: We report 7 eyes from 6 cases and combine these data with 7 previous case reports identified by a search of PubMed. RESULTS: DM detachment occurred at a median of 25 years (range, 7-33 years) after PK. One individual had bilateral detachments. There was typically a mild ocular discomfort accompanied in some cases by a rapid onset of visual blur. Cases were often treated for allograft rejection before a DM detachment was suspected and confirmed by optical coherence tomography. Detachments were limited to the donor tissue in 11 eyes, but a DM break was identified at the time of onset in only 4 eyes. Thinning of the host corneal rim with ectasia was reported in 8 eyes (57%). In 3 eyes, the detachment resolved spontaneously, but in 2 eyes, a detachment was still present at 12 months. Gas tamponade to reattach the DM was performed in 9 eyes and was effective in 4 eyes. Five eyes underwent a repeat PK or endothelial keratoplasty. Histology showed fibroblastic proliferation on the stromal surface of the folded DM. CONCLUSIONS: The cause for DM detachment many years after PK is unknown, although progressive thinning of the host cornea and secondary graft ectasia may be implicated. Gas tamponade can be effective, but a repeat keratoplasty might be necessary. DM detachment should be included in the differential diagnosis for late-onset corneal edema after PK.

Spontaneous Descemet Membrane Detachment After Penetrating Keratoplasty-Clinical Presentation and Outcome of Air/Gas Descemetopexy.

PURPOSE: To describe the clinical characteristics and treatment of spontaneous Descemet membrane (DM) detachment occurring decades after penetrating keratoplasty (PK). METHODS: A multicenter interventional case series design was used. We reviewed the medical records of 4 patients with a history of PK presenting with spontaneous DM detachment at 3 university hospitals in Israel and an ocular surgery institute in The Netherlands in 2016 to 2019. Patient demographic and clinical data, postoperative best corrected visual acuity, findings on preoperative and postoperative anterior segment optical coherence tomography (AS-OCT), and graft survival were recorded. RESULTS: Patients were aged 46 to 50 years. All had undergone PK for keratoconus 20 to 26 years previously. Patients presented within 18 to 180 days of onset of visual disturbance. Symptoms included sudden painless visual loss (2 patients), gradual visual loss and foreign body sensation (1 patients), and visual loss not otherwise specified (1 patient). Slit-lamp examination showed corneal edema, and AS-OCT showed DM detachment of variable extent. In 2 patients, the initial diagnosis was graft rejection and failure. Treatment consisted of anterior chamber injection of air (n = 3) or 20% SF6 (n = 1). In 3 patients, the DM reattached and the cornea regained its clarity. The fourth patient had persistent DM detachment that required repeated PK. CONCLUSIONS: Spontaneous DM detachment can mimic late graft failure in patients after PK. If diagnosed early, DM reattachment may be performed by air/gas injection, avoiding repeated keratoplasty. Eyes with presumed late penetrating graft rejection or failure should be examined by AS-OCT to exclude DM detachment.

The role of multiparametric ultrasound in the diagnosis of paediatric scrotal pathology.

Multiparametric ultrasound (MPUS), combining conventional techniques (greyscale and colour Doppler ultrasound), ultrasound strain elastography, and contrast-enhanced ultrasound (CEUS), has been successfully used in the assessment of adult scrotal pathology. Contrast-enhanced ultrasound can confidently establish testicular tissue vascularity even in the small-volume paediatric testis. Elastography provides further assessment of tissue stiffness, potentially adding useful diagnostic information. In children, ultrasonography is particularly advantageous, being safe, radiation-free and negating the need for sedation or general anaesthesia during the imaging evaluation. In this review article, we aim to familiarise readers with the MPUS scanning protocol used for paediatric scrotal examination and provide an overview of scrotal MPUS features, with particular focus to clinical indications where MPUS may be advantageous over conventional ultrasonography.

Intravitreal Recombinant Tissue Plasminogen Activator and Sulphur Hexafluoride Gas for Submacular Haemorrhage Displacement in Age-Related Macular Degeneration: Looking behind the Blood.

PURPOSE: To evaluate the effectiveness of recombinant tissue plasminogen activator (rtPA) and sulphur hexafluoride gas (SF6) intravitreal injection for the displacement of large submacular haemorrhages (SMH) secondary to neovascular age-related macular degeneration and for guiding the selection of additional treatments or observations for choroidal neovascularization (CNV). METHODS: The medical records of consecutive patients with recent-onset, large SMH, treated at Sacro Cuore Hospital from January 2004 to May 2016, were retrospectively analysed. All eyes underwent a 0.05-mL intravitreal injection of 50 µg rtPA, 0.3 mL of 100% SF6, and then face-down positioning. Afterwards, the eyes received additional treatments for CNV or observation, based on the severity and extent of the underlying pathology. The multimodal imaging features revealed after blood displacement were analysed and then correlated to the treatment selected as a second therapeutic option. RESULTS: A total of 96 eyes met the inclusion criteria and was evaluated in this study. SMH was displaced from the fovea in the majority of the eyes (76%), allowing several diagnostic tools to evaluate the underlying macular features. In 19 cases (19.8%) exhibiting severe macular damage, no additional treatment was applied. In the remaining eyes, subsequent treatments included anti-vascular endothelial growth factor injections (44.8%), photodynamic therapy (n = 2), and submacular surgery (35.4%). Statistically significant correlations were found between the macular findings revealed after blood displacement and the additional treatments or observations selected for the underlying disease. The mean follow-up was 35 months. Improvements in visual acuity were statistically significant up to 3 years. CONCLUSION: Intravitreal rtPA and gas injection was found to be effective for the displacement of large SMH, allowing postoperative diagnostic testing, and thus guiding the opportunity to apply further treatments. The addition of subsequent individualized treatments may allow long-term visual gain in selected cases.

Anterior chamber aqueous flare is not a predictor for surgical closure of full-thickness idiopathic macular holes.

PURPOSE: To investigate the predictive value of preoperative anterior chamber aqueous flare levels measured by laser flare photometry for surgical success of idiopathic macular holes in addition to preoperative anatomic characteristics. METHODS: Records of 105 consecutive eyes with full-thickness idiopathic macular holes which underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride 20% (SF620%) endotamponade were reviewed retrospectively. All patients underwent preoperative measurements of anterior chamber aqueous flare and anatomical idiopathic macular hole characteristics evaluated by optical coherence tomography: macular hole inner opening diameter, macular hole minimum linear diameter, macular hole base diameter, and macular hole height. Best-corrected visual acuity results were recorded pre- and postoperatively. RESULTS: In 17 (16.2%) of 105 eyes primary closure of idiopathic macular hole failed, whereas in 88 eyes (83.8%) closure was achieved. Between both groups, preoperative macular hole minimum linear diameter (p = 0.001) and macular hole inner opening diameter (p = 0.006) were statistically different. Failure rates were significantly lower in eyes with macular hole minimum linear diameter < 400 µm (7.4% vs 32.4%; p = 0.013) and preoperative macular hole minimum linear diameter showed moderate correlation with pre- and postoperative best-corrected visual acuity results (r = 0.512; p < 0.001; r = 0.612; p < 0.001). Mean anterior chamber aqueous flare of 11.5 ± 9.9 pc/ms in eyes with anatomical closure and 11.8 ± 6.4 pc/ms in unclosed cases was comparable (p = 0.28) and did not correlate with anatomical or functional results. CONCLUSION: Eyes with idiopathic macular hole ⩾ 400 µm in size have a significantly higher failure rate following standardized pars plana vitrectomy with internal limiting membrane peeling and SF620% endotamponade. Preoperative macular hole minimum linear diameter and macular hole inner opening diameter seem to be associated with surgical outcome in idiopathic macular hole, whereas anterior chamber aqueous flare level does not provide additional predictive value.