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 .

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.

INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 µm vs. 780.2 µm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 µm vs. 326.5 µm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

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.

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.

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.

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.

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.

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.

Effect of Gas Tamponade on the Intraocular Lens Position and Refractive Error after Phacovitrectomy: A Swept-Source Anterior Segment OCT Analysis.

PURPOSE: To investigate the intraocular lens (IOL) position and refractive outcomes after cataract surgery and phacovitrectomy using swept-source anterior segment OCT (SS-ASOCT). DESIGN: Retrospective case series. PARTICIPANTS: Patients underwent cataract surgery (group A: 34 eyes), phacovitrectomy without gas tamponade (group B: 20 eyes), and phacovitrectomy with gas tamponade (group C: 22 eyes). METHODS: Various parameters associated with the anterior chamber and lens were measured by SS-ASOCT (CASIA2; Tomey Corp, Nagoya, Japan) before and after surgery. Axial lengths were measured by optical biometry (IOLMaster; Carl Zeiss, Oberkochen, Germany). The refraction (spherical equivalent) was measured 1 week and 1 month after surgery. MAIN OUTCOME MEASURES: Refractive outcomes and the parameters measured by SS-ASOCT were statistically evaluated. RESULTS: The overall mean median absolute error (MedAE) was 0.34 diopters (D) at 1 month postoperatively. The MedAE was greater in group C (0.47 D) than in group A (0.31 D) and group B (0.20 D). The overall mean refractive prediction error (ME) was -0.22±0.62 D at 1 month postoperatively. The ME was significantly greater in group C (-0.82±0.64 D) than in group A (0.08±0.39 D) and group B (-0.07±0.45 D) (P < 0.001, P < 0.001), indicating a greater myopic shift in group C. The forward movement of the IOL position was significantly correlated with a greater ME at 1 month (R = 0.53, P < 0.001). CONCLUSIONS: Forward fixation of the IOL caused myopic refractive errors even after the gas had disappeared in eyes that underwent phacovitrectomy with gas tamponade.

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.

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.

HUMAN AMNIOTIC MEMBRANE TO CLOSE RECURRENT, HIGH MYOPIC MACULAR HOLES IN PATHOLOGIC MYOPIA WITH AXIAL LENGTH OF ≥30 mm.

PURPOSE: To assess the effectiveness of the human amniotic membrane plug for recurrent high myopic macular hole (MH) that already underwent pars plana vitrectomy with internal limiting membrane peeling and gas endotamponade. METHODS: Sixteen eyes of 16 patients with recurrent high myopic MH were enrolled. A 23-gauge pars plana vitrectomy was performed. Human amniotic membrane plugs were implanted under the neuroretina inside the MH. Twenty percent sulfur hexafluoride or air was used as endotamponades. The patients were instructed to maintain facedown position for 5 days after surgery. RESULTS: Optical coherence tomography examinations showed that the MHs closed in 15 of the 16 patients (93.75%) 2 weeks after one surgical intervention, and in 100% of patients after second intervention. Mean best-corrected visual acuity improved from 1 logarithm of the minimum angle of resolution (20/200) to 0.67 logarithm of the minimum angle of resolution (20/100) 6 months after surgery. Best-corrected visual acuity remained stable during the 12-month follow-up. One patient had human amniotic membrane plug dislocation after gas absorption that needed a second intervention with new AM plug implantation. No adverse events were reported during the 12-month follow-up. CONCLUSION: The first case series of recurrent high myopic MH was reported, assessing the effectiveness of the human amniotic membrane plug to close recurrent MHs in pathologic myopia. All the cases were successful with encouraging best-corrected visual acuity recovery.

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.

Clinical utility, dose determination, and safety of ocular contrast-enhanced ultrasonography in horses: A pilot study.

OBJECTIVE: To determine efficacy of contrast-enhanced ultrasonography (CEUS) using different sulfur hexafluoride (SF6) doses to assess blood flow and perfusion in equine eyes and to evaluate safety of SF6 in horses. PROCEDURES: Ocular B-mode and contrast-enhanced ultrasonography were performed bilaterally in nine sedated university-owned horses. Intravenous SonoVue® bolus injections of 5, 10, 15, 20, 25, and 30 mL were administered for 2/18, 5/18, 6/18, 3/18, 1/18, and 1/18 eyes, respectively. Doses were increased based on ascending bodyweight. Each eye within one horse was examined utilizing a different dose. Qualitative blood flow and quantitative perfusion were analyzed. Heart and respiratory rates were monitored nonsedated, sedated, and during first and second minutes of CEUS. RESULTS: Qualitative contrast enhancement (CE) was visible in 7/9 animals. Quantitative CE was measurable bilaterally in four horses, unilaterally in three individuals, and not detected in two animals. In all horses with unilateral CE, the positive eye received the higher dose. Fifteen mL dose resulted in significantly shorter time to peak than 10 mL (P < .05). Peak intensity, maximum signal increase, and corresponding area under the curve were significantly higher for 15 and 20 mL doses compared with 10 mL (P < .05). Uveal and retinal tissues were enhanced frequently. Twenty-five and 30 mL doses revealed no CE. Only sedation reduced heart rates significantly (P < .05). Clinically relevant changes in respiratory rates or adverse reactions following SF6 application were not observed. CONCLUSIONS: Contrast enhancement was in most instances dose-dependent. Fifteen mL appeared appropriate to assess equine ocular perfusion. The reliability in horses remains questionable; however, CEUS was well-tolerated.

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.

The Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT).

PURPOSE: The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o'clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina. METHODS: Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively. MAIN OUTCOME MEASURES: The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success. RESULTS: One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P < 0.001). CONCLUSIONS: Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.

19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:343-354.

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES: We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS: We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS: The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS: We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results.

Myocardial contrast echocardiography in the diagnosis of postoperative takotsubo myocardiopathy: case report and literature review.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is a brief ventricular dysfunction that usually occurs after emotional or physical stress. Here, we report a patient who underwent cardiac surgery and then developed TCM during the postoperative period. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital complaining of chest tightness, palpitations and dyspnoea after activity. An echocardiogram performed by our hospital showed rheumatic heart disease (severe mitral stenosis and regurgitation) with normal cardiac function and wall motion. After mitral valve replacement, this patient developed heart failure with low blood pressure and tachycardia. Urgent bedside echocardiography demonstrated akinesis in the middle and apical segments of the left ventricle and a depressed ejection fraction (EF) of 36%. Myocardial contrast echocardiography (MCE) showed similar enhancement intensity in the basal, middle and apical segments. Quantitative analysis showed approximately equivalent maximum intensity in these regions. The diagnosis was considered TCM instead of myocardial infarction. Then, an intra-aortic balloon pump was inserted to maintain effective circulation and reduce the postcardiac load. Given ventilation therapy, postoperative anticoagulation therapy and anti-infection treatment, the patient recovered quickly. In the follow-up examination, the patient remained asymptomatic and showed normalization of ventricular wall motion in the apical segment. CONCLUSION: This report presents a case of TCM in which MCE was used to demonstrate intact microvascular perfusion despite apical akinesis. This report might support the use of MCE as a substitute for invasive coronary angiography.

Intravenous Contrast-Enhanced Ultrasound for Assessing and Grading Postoperative Recurrence of Crohn's Disease.

PURPOSE: The aim was to investigate the contribution of contrast-enhanced ultrasound (CEUS) to improve the results of US in the evaluation of recurrence in postsurgical Crohn's disease (CD) and establish its role in the assessment of the severity. METHODS: Anastomotic site was assessed in 108 postsurgical CD patients with B-mode, color Doppler and CEUS. Bowel wall thickness (WT), transmural complications or stenosis, color Doppler grade, and bowel wall contrast enhancement (BWCE)-using time-intensity curves-were correlated with endoscopic Rutgeerts score. A receiver operating characteristic (ROC) curve was built to establish the best cutoff to predict recurrence and the severity. A US scoring system was elaborated in order to determine the grade of recurrence. RESULTS: Ileocolonoscopy detected recurrence in 90 (83.3%) subjects and severe recurrence in 62. WT ≥ 3 mm had an accuracy of 90.7% in the detection of endoscopic recurrence. The combination of parameters-WT ≥ 3 mm and BWCE (≥ 46%)-demonstrated similar accuracy (90.7%). A WT ≥ 5 mm showed the best specificity (100%) for the diagnosis of recurrence and a WT ≥ 6 mm the best specificity (95.7%) for the detection of severe recurrence. The combination of sonographic parameters-WT ≥ 6 mm or WT between 5 and 6 mm with BWCE ≥ 70%, or complications-obtained the best results grading the recurrence (sensitivity, specificity, and accuracy of 90.3%, 87%, and 88.9%, respectively). CONCLUSIONS: US shows high sensitivity and specificity for the diagnosis of postsurgical recurrence. When combined with CEUS, it can improve the detection of severe recurrence.