Role of HIF1α and HIF2α in Cre Recombinase-Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization.

CreTrp1 mice are widely used for conditional retinal pigment epithelium (RPE) gene function studies. Like other Cre/LoxP models, phenotypes in CreTrp1 mice can be affected by Cre-mediated cellular toxicity, leading to RPE dysfunction, altered morphology and atrophy, activation of innate immunity, and consequent impairment of photoreceptor function. These effects are common among the age-related alterations of RPE that feature in early/intermediate forms of age-related macular degeneration. This article characterizes Cre-mediated pathology in the CreTrp1 line to elucidate the impact of RPE degeneration on both developmental and pathologic choroidal neovascularization. Nonredundant roles of the two major components of the hypoxia-inducible factor (HIF) family of transcription regulators, HIF1α and HIF2α, were identified. Genetic ablation of Hif1a protected against Cre-induced degeneration of RPE and choroid, whereas ablation of Hif2a exacerbated this degeneration. Furthermore, HIF1α deficiency protected CreTrp1 mice against laser-induced choroidal neovascularization, whereas HIF2α deficiency exacerbated the phenotype. Cre-mediated degeneration of the RPE in CreTrp1 mice offers an opportunity to investigate the impact of hypoxia signaling in the context of RPE degeneration. These findings indicate that HIF1α promotes Cre recombinase-mediated RPE degeneration and laser-induced choroidal neovascularization, whereas HIF2α is protective.

Retinal detachment after post-operative endophthalmitis: clinical characteristics, outcomes and risk factors.

PURPOSE: To describe clinical characteristics, risk factors, and outcomes of rhegmatogenous retinal detachment (RRD) following treatment of postoperative endophthalmitis (PE). METHODS: Analysis of cross-referenced data from two service reviews of patients with RRD and bacterial PE treated between 01/01/2013 and 01/07/2020. The main outcome measure was final best-corrected visual acuity (BCVA). Secondary measures include proportion of patients with BCVA of ≤ 0.3 logMAR and ≥ 1.0 logMAR, rate of phthsis, and rate of eye removal. RESULTS: Ninety-four cases of PE were analysed finding 21 cases of RRD (22%). Seven (35%) experienced recurrent RRD. Seven eyes (35%) were left with permanent silicone oil fill. All RRD cases had vitrectomy. After PE with RRD the median BCVA was 1.1 logMAR, compared with 0.4 logMAR for PE without RRD (p < 0.04). Fifty-seven percent (12/21) of RRD eyes attained BCVA of ≥ 1.0 logMAR vs. 29% (21/73) of PE without RRD (p = 0.01). Nineteen percent (4/21) of eyes with RRD attained BCVA of ≤ 0.3 logMAR, whereas those without RRD did so in 43% (31/73) of cases (p = 0.02). Five eyes with RRD (24%) and 2 eyes without RRD (3%) developed phthisis (p < 0.01). Three non-RRD cases required removal of the eye (4%, p = 0.46). Higher bacterial virulence was associated with worse final BCVA (2.1 logMAR vs. 0.3 logMAR; p < 0.01). RRD rate did not differ by bacterial virulence (OR 1.9; CI95: 0.6-6.9; p = 0.24). CONCLUSIONS: RRD following PE leads to worse clinical outcomes. Eyes which developed RRD were more likely to have undergone vitrectomy. Final BCVA was worse in cases with more virulent micro-organisms.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization.

[Figure: see text].

Late neuroprogenitors contribute to normal retinal vascular development in a Hif2a-dependent manner.

In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of this important relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show in mouse that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a (Hif2a). By Cre-lox gene excision, we show that Hif2a in retinal neuroprogenitor cells upregulates the expression of the pro-angiogenic mediators vascular endothelial growth factor and erythropoietin, whereas it locally downregulates the angiogenesis inhibitor endostatin. Importantly, absence of Hif2a in retinal neuroprogenitor cells causes a marked reduction of proliferating endothelial cells at the angiogenic front. This results in delayed retinal vascular development, fewer major retinal vessels and reduced density of the peripheral deep retinal vascular plexus. Our findings demonstrate that retinal neuroprogenitor cells are a crucial component of the developing neurovascular unit.

Comparison of Perfluorodecalin and Silicone Oil as Initial Tamponade for Giant Retinal Tear-Associated Retinal Detachment.

INTRODUCTION: To compare visual outcomes and complication rates of giant retinal tear-associated retinal detachment (GRT-RD) cases treated with short-term perfluorodecalin (PFD) tamponade versus silicone oil (SiO). METHODS: Database analysis of patients with GRT-RD operated on in the period from 1 January 2014 to 31 December 2019. RESULTS: Forty-five patients were operated for GRT-RD using PFD or SiO during this period. Two children, 7 patients receiving gas tamponade, and 2 lost to follow-up were excluded. Eighteen eyes (40%) received PFD and 27 (60%) received SiO. There were 15/18 (83%) macula-sparing cases in the PFD group and 18/27 (67%) in the SiO group (p = 0.13). The mean duration of oil tamponade was 91 days for SiO and 7.6 days for PFD (p < 0.0001). The mean length of follow-up was 274.5 days for PFD and 668.9 days for SiO. The mean BCVA was 6/18 (63.4 ± 26.0 ETDRS letters) for SiO and 6/12 (72.9 ± 12.7 ETDRS letters) for PFD (p = 0.42). Analysing macula-sparing pseudophakic eyes, the BCVA was 6/12 (67.4 ± 25.9 letters, n = 18) for SiO eyes and 6/9 (76.8 ± 9.9 letters, n = 11) for PFD eyes (p = 0.54). The recurrence rate was 22% (6/27) for SiO and 6% (1/18) for PFD (p = 0.12). The rate of cystoid macular oedema (CMO) was 22% for SiO and 22% for PFD. Epiretinal membrane (ERM) was found in 26% of SiO cases and 22% of PFD cases. Loss of vision after oil removal was not observed. Seven eyes (26%) receiving SiO and none receiving PFD developed chronic ocular hypertension (OHT) (p = 0.02). CONCLUSIONS: Short-term tamponade with PFD for GRT-RD appears similar to tamponade with SiO in terms of the visual outcomes and complication rates.

Stabilization of myeloid-derived HIFs promotes vascular regeneration in retinal ischemia.

The retinal vasculature is tightly organized in a structure that provides for the high metabolic demand of neurons while minimizing interference with incident light. The adverse impact of retinal vascular insufficiency is mitigated by adaptive vascular regeneration but exacerbated by pathological neovascularization. Aberrant growth of neovessels in the retina is responsible for impairment of sight in common blinding disorders including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration. Myeloid cells are key players in this process, with diverse roles that can either promote or protect against ocular neovascularization. We have previously demonstrated that myeloid-derived VEGF, HIF1, and HIF2 are not essential for pathological retinal neovascularization. Here, however, we show by cell-specific depletion of Vhl in a mouse model of retinal ischemia (oxygen-induced retinopathy, OIR) that myeloid-derived HIFs promote VEGF and bFGF expression and enhance vascular regeneration in association with improved density and organization of the astrocytic network.

A Study of the Natural History of Vitreomacular Traction Syndrome by OCT.

PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS) in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS with no other ocular comorbidity. METHODS: Patients with VMTS were identified from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and patient notes were reviewed over a minimum period of 6 months. Data collected included patient demographics, best-corrected visual acuity, and OCT features of vitreomacular adhesion. Contingency tests and binary logistic modeling were used to identify baseline predictors of stability and progression. MAIN OUTCOME MEASURES: The rates of spontaneous resolution (defined by release of traction), progression to full-thickness macular hole, and surgical intervention were analyzed. RESULTS: Presenting visual acuity was 0.3±0.3 logMAR units. The mean length of follow-up was 17.4±12.1 months. During this period, VMTS persisted in 60% and resolved in 20% (occurring on average at 15 months). Of the remainder, 12% developed a macular hole and 8% elected to proceed with surgery for symptoms. Focal adhesion <1500 µm was present in 87%. A premacular membrane with macular pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal thickness remained unchanged. The relative risk of resolution increased in those cases with better presenting visual acuities, lesser foveal thicknesses, and no associated PMMs; vision significantly improved in those cases with resolution. CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual acuities did not deteriorate significantly over the study period unless patients developed a full-thickness macular hole or required surgical intervention for symptoms. Resolution spontaneously occurred in 20%, with an improvement in vision.

Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization--Brief Report.

OBJECTIVE: Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined. APPROACH AND RESULTS: We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy. CONCLUSIONS: The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies.

IL-4 regulates specific Arg-1(+) macrophage sFlt-1-mediated inhibition of angiogenesis.

One of the main drivers for neovascularization in age-related macular degeneration is activation of innate immunity in the presence of macrophages. Here, we demonstrate that T helper cell type 2 cytokines and, in particular, IL-4 condition human and murine monocyte phenotype toward Arg-1(+), and their subsequent behavior limits angiogenesis by increasing soluble fms-like tyrosine kinase 1 (sFlt-1) gene expression. We document that T helper cell type 2 cytokine-conditioned murine macrophages neutralize vascular endothelial growth factor-mediated endothelial cell proliferation (human umbilical vein endothelial cell and choroidal vasculature) in a sFlt-1-dependent manner. We demonstrate that in vivo intravitreal administration of IL-4 attenuates laser-induced choroidal neovascularization (L-CNV) due to specific IL-4 conditioning of macrophages. IL-4 induces the expression of sFlt-1 by resident CD11b(+) retinal microglia and infiltrating myeloid cells but not from retinal pigment epithelium. IL-4-induced suppression of L-CNV is not prevented when sFlt-1 expression is attenuated in retinal pigment epithelium. IL-4-mediated suppression of L-CNV was abrogated in IL-4R-deficient mice and in bone marrow chimeras reconstituted with myeloid cells that had undergone lentiviral-mediated shRNA silencing of sFlt-1, demonstrating the critical role of this cell population. Together, these data establish how lL-4 directly drives macrophage sFlt-1 production expressing an Arg-1(+) phenotype and support the therapeutic potential of targeted IL-4 conditioning within the tissue to regulate disease conditions such as neovascular age-related macular degeneration.

Flow cytometric analysis of inflammatory and resident myeloid populations in mouse ocular inflammatory models.

Myeloid cells make a pivotal contribution to tissue homeostasis during inflammation. Both tissue-specific resident populations and infiltrating myeloid cells can cause tissue injury through aberrant activation and/or dysregulated activity. Reliable identification and quantification of myeloid cells within diseased tissues is important to understand pathological inflammatory processes. Flow cytometry is a valuable technique for leukocyte analysis, but a standardized flow cytometric method for myeloid cell populations in the eye is lacking. Here, we validate a reproducible flow cytometry gating approach to characterize myeloid cells in several commonly used models of ocular inflammation. We profile and quantify myeloid subsets across these models, and highlight the value of this strategy in identifying phenotypic differences using Ccr2-deficient mice. This method will aid standardization in the field and facilitate future investigations into the roles of myeloid cells during ocular inflammation.

Diagnostic accuracy of magnetic resonance imaging (MRI) prostate imaging reporting and data system (PI-RADS) scoring in a transperineal prostate biopsy setting.

OBJECTIVES: To determine the sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) for significant prostate cancer with transperineal sector biopsy (TPSB) as the reference standard. PATIENTS AND METHODS: The study included consecutive patients who presented for TPSB between July 2012 and November 2013 after mpMRI (T2- and diffusion-weighted images, 1.5 Tesla scanner, 8-channel body coil). A specialist uro-radiologist, blinded to clinical details, assigned qualitative prostate imaging reporting and data system (PI-RADS) scores on a Likert-type scale, denoting the likelihood of significant prostate cancer as follows: 1, highly unlikely; 3, equivocal; and 5, highly likely. TPSBs sampled 24-40 cores (depending on prostate size) per patient. Significant prostate cancer was defined as the presence of Gleason pattern 4 or cancer core length ≥6 mm. RESULTS: A total of 201 patients were included in the analysis. Indications were: a previous negative transrectal biopsy with continued suspicion of prostate cancer (n = 103); primary biopsy (n = 83); and active surveillance (n = 15). Patients' mean (±sd) age, prostate-specific antigen and prostate volumes were 65 (±7) years, 12.8 (±12.4) ng/mL and 62 (±36) mL, respectively. Overall, biopsies were benign, clinically insignificant and clinically significant in 124 (62%), 20 (10%) and 57 (28%) patients, respectively. Two of 88 men with a PI-RADS score of 1 or 2 had significant prostate cancer, giving a sensitivity of 97% (95% confidence interval [CI] 87-99) and a specificity of 60% (95% CI 51-68) at this threshold. Receiver-operator curve analysis gave an area under the curve of 0.89 (95% CI 0.82-0.92). The negative predictive value of a PI-RADS score of ≤2 for clinically significant prostate cancer was 97.7% CONCLUSION: We found that PI-RADS scoring performs well as a predictor for biopsy outcome and could be used in the decision-making process for prostate biopsy.

PRIMARY SCLERAL BUCKLING FOR PEDIATRIC RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the anatomical outcomes of primary scleral buckling (SB) procedures for pediatric rhegmatogenous retinal detachments. METHODS: Retrospective consecutive case series. One hundred and four eyes of 99 consecutive nonselected pediatric patients undergoing primary SB were identified. Baseline factors recorded were demographics, presenting clinical examination findings, previous ocular surgery, predisposing factors. Intraoperative factors recorded were the type of buckle, number and distribution of retinal breaks, number of retinal quadrants detached, macular status (involved vs. uninvolved), the use of subretinal fluid drainage, and surgical complications. Anatomical reattachment rate at last follow-up. Subgroup analysis was carried out to identify any predisposing factors for failure of primary surgery, effect of age on outcome, intraoperative pathology, effect of posterior versus anterior SB, and redetachment and secondary-procedure complications specific to SB. RESULTS: The initial surgery was segmental SB alone in 87 eyes (83.6%). Retinal reattachment was achieved with 1 operation in 73% (76 of 104 eyes). Of the 28 cases that redetached, 14 eyes underwent a repeat SB procedure (success rate of this second operation: 85.7% [12 of 14 eyes]), 13 eyes underwent vitrectomy (success rate of this second operation: 38.4% [5 of 13 eyes]), and 1 case was not reoperated. Overall, the final success rate was 94% (98 of 104 eyes). Factors associated with a statistically significant increased risk of failure included more than one break; three or more quadrants of detachment; horseshoe tears; no breaks seen on preoperative examination; Stickler syndrome. CONCLUSION: In selected cases, primary SB is an effective treatment for pediatric, rhegmatogenous retinal detachment.

RHEGMATOGENOUS RETINAL DETACHMENT AFTER INJECTION OF TISSUE PLASMINOGEN ACTIVATOR AND GAS FOR SUBMACULAR HEMORRHAGE SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The purpose of this study was to describe the rate, clinical characteristics, and outcomes of rhegmatogenous retinal detachment (RRD) after injection of tissue plasminogen activator (TPA) and gas for submacular hemorrhage displacement. METHODS: Retrospective analysis of consecutive cases developing RRD after TPA injection and gas for submacular hemorrhage displacement. The rate of RRD was calculated, and a description of RRD clinical characteristics was performed. Anatomic and visual outcomes after RRD repair were analyzed. RESULTS: Ninety eyes of 90 patients were analyzed. Tissue plasminogen activator was given intravitreally in 53 eyes (59%) and subretinally in 37 eyes (41%). RRD occurred in 6 of 90 eyes (7%). Of these, one had intravitreal TPA and five had vitrectomy with subretinal TPA ( P = 0.04). The mean age was 75 (64-93) years. The median time of RRD occurrence was 42 (1-134) days. All cases had macular involvement. Two cases had PVR at presentation. Vitrectomy was performed in all cases and silicone oil used in five, all of which resulted in permanent silicone oil retention. One case (17%) achieved primary single surgery success. The median final visual acuity was 1.8 logMAR (20/1,260 Snellen). CONCLUSION: The RRD rate after submacular hemorrhage displacement was 7% in our case series. Rhegmatogenous retinal detachment occurred more commonly after vitrectomy with subretinal TPA injection. The visual and anatomic outcomes were poor, with a high rate of retained silicone oil and recurrent RRD.

Using spectral-domain optical coherence tomography imaging to identify the presence of retinal silicone oil emulsification after silicone oil tamponade.

PURPOSE: To describe small hyperreflective areas using spectral-domain optical coherence tomography (SD-OCT) imaging in eyes that have had silicone oil tamponade. METHODS: Retrospective case series of 11 eyes of 11 patients. The authors retrospectively identified patients who underwent vitrectomy and silicone oil tamponade secondary to a rhegmatogenous retinal detachment (nine patients), panuveitis with retinal necrosis (one patient), or recurrent full-thickness macular hole surgery (one patient) who had manifestations of silicone oil emulsion on SD-OCT imaging. Patients were monitored during the postoperative period by clinical examination and using SD-OCT. A model eye in which emulsified silicone oil had been injected in the anterior chamber was used to obtain anterior segment SD-OCT images for comparison. RESULTS: The mean age of our patients was 50 years (range, 39-76 years). In eight eyes, the SD-OCT examination was carried out after silicone oil removal, and in three eyes, the SD-OCT examination was carried out with the oil in situ. Of the nine eyes treated for rhegmatogenous retinal detachment, five had a relieving retinectomy for advanced anterior proliferative vitreoretinopathy or for traumatic retinal incarceration (one eye). The eye treated for full-thickness macular hole had a vitrectomy, internal limiting membrane peel, and silicone oil injection for recurrent macular hole. Ten eyes showed hyperreflective, spherical, tiny droplets using SD-OCT imaging. These were thought to represent silicone oil droplets intraretinally or underneath epiretinal membranes, and one eye showed hyperreflective areas subretinally (retina detached). One additional patient was found to have tiny intravitreal silicone oil droplets after silicone oil removal. Similarly, the silicone oil appeared as multiple hyperreflective spherical droplets as detected by SD-OCT. Anterior segment studies of silicone oil emulsification in the experimental model revealed a similar appearance to that seen with in vivo SD-OCT imaging. CONCLUSION: The authors have found small hyperreflective areas intraretinally, subretinally, and underneath epiretinal membranes on SD-OCT in eyes that have had silicone oil tamponade for a variety of indications. The authors have seen a similar appearance when silicone oil emulsification is examined in vivo. The authors conclude that the hyperreflective areas are likely (but not certain) to be very small bubbles of emulsified silicone. Further studies are required to determine the incidence, clinicopathologic, and functional significance of probable silicone oil emulsification and deposition within the retinal layers.

Effectiveness of semi-quantitative multiphase dynamic contrast-enhanced MRI as a predictor of malignancy in complex adnexal masses: radiological and pathological correlation.

OBJECTIVES: To determine whether threshold criteria using semi-quantitative multiphase-dynamic contrast-enhanced magnetic resonance imaging (DCE- MRI) can improve prediction of malignancy in complex adnexal masses. METHODS: MRI features of 70 complex adnexal masses with enhancing components in 63 patients were reviewed and correlated with histopathology (n = 67) or radiological follow-up (n = 3). Masses were categorised as benign (n = 34) or borderline/invasive malignant (n = 36). Borderline lesions (n = 6) were also analysed separately. Using the semi-quantitative breast analysis software, regions of interest were drawn around the most avidly enhancing component of each lesion. Maximum absolute enhancement of signal intensities (SI(max)), maximum relative enhancement (SI(rel)) and wash-in rate (WIR) were recorded. Optimal threshold criteria were established to predict borderline/invasive malignancy. RESULTS: There was a significant difference in mean SI(max) (P < 0.05), SI(rel) (P < 0.01) and WIR (P < 0.001) between benign and borderline/invasive malignant groups. A cut-off WIR ≥ 9.5 l/s had a specificity of 88% and positive predictive value of 86% for predicting malignancy, significantly better than conventional MRI (62%, P < 0.01). WIR <8.2 l/s had a negative predictive value of 94%. CONCLUSION: Threshold criteria using semi-quantitative multiphase DCE-MRI improves specificity in the prediction of malignancy in complex adnexal masses with enhancing components and is complementary to standard qualitative assessment. KEY POINTS: Semi-quantitative DCE-MRI threshold criteria are effective for predicting ovarian malignancy. The surgical approach may be altered depending on DCE-MRI threshold criteria analysis. Borderline tumours demonstrate significant overlap with benign lesions using DCE-MRI threshold criteria.

Skull base osteomyelitis and potential cerebrovascular complications in children.

Skull base osteomyelitis is an aggressive, life-threatening infection that can be challenging to diagnose and treat. It occurs predominantly in elderly immunocompromised patients, but it has also been reported in children with normal immunological status. Typical skul base osteomyelitis arises as a complication to ear infection mainly involving the temporal bone and is usually caused by Pseudomonas aeruginosa. Atypical or central skul base osteomyelitis originates from paranasal infections, is primarily centred on the clivus and is usually caused by Aspergillus, Pseudomonas, Salmonella or Staphylococcus species. Potential complications include retropharyngeal abscesses, cranial neuropathies, meningitis, intracranial abscesses, sinovenous thrombosis, and carotid artery involvement with or without ischemic infarcts. The purpose of this pictorial essay is to illustrate the spectrum of imaging findings and potential complications of skul base osteomyelitis.

Unilateral Duplicated Collecting System Identified During Pelvic Lymphadenectomy: A Case Report and Literature Review.

Anatomic variations can be an additional challenge for any surgeon, especially in complicated surgical procedures, and they could lead to complications if not identified timely. We present a case report of an incidental intraoperative finding of unilateral duplicated ureter, identified during pelvic lymphadenectomy for a patient who underwent surgical treatment for ovarian cancer. Also, we include an update on this anatomic variation following the literature review. The importance of a systematic approach in the identification of the relevant anatomy and landmarks, taking into consideration the variation of the duplicated ureter, is emphasized in this paper and may contribute beneficially to the experience of surgeons operating in this field.

The Risk of Sympathetic Ophthalmia after Vitreoretinal Surgery.

PURPOSE: To investigate the clinical course and outcomes of sympathetic ophthalmia (SO) and correlate these with the nature of the inciting event and the number of vitreoretinal (VR) procedures undergone by patients. DESIGN: A retrospective case review. SUBJECTS: All patients diagnosed with SO who had been treated or monitored at a single center over a 15-year period. METHODS: A search of the electronic patient record system at Moorfields Eye Hospital, London, over a 15-year period (between January 2000 and December 2015) was carried out using the search terms "sympathetic," "ophthalmia," and "ophthalmitis." Sixty-one patients with available records were identified, and data were collected from their complete electronic and paper records. MAIN OUTCOME MEASURES: The main outcome measures were best-corrected visual acuity at 1 year and at the end of follow-up and the number of VR surgical procedures preceding the diagnosis of SO. Data on patient age, sex, disease duration, ocular and systemic manifestations, ocular complications, retinal angiography, and treatment were also collected. RESULTS: There was a wide age range at presentation (2-84 years), and the length of follow-up ranged from 1 to 75 years. The first ocular event was trauma in 40 patients and surgery in 21 patients. Vitreoretinal surgery accounted for 13 of the 21 (62%) surgical first-event triggers. Twenty-three of 61 (38%) patients underwent VR surgery (1-7 operations) at some point before diagnosis. Surgical details were available for 15 patients, who had undergone a total of 25 VR procedures. Based on the surgical activity of the unit, the risk of developing SO after a single VR procedure was estimated to be 0.008%, rising to 6.67% with 7 procedures. A total of 23 (38%) patients experienced a decrease in acuity at the end of the follow-up period, vs. 9 (15%) patients experiencing an improvement and 18 (30%) remaining unchanged. CONCLUSIONS: We feel that the most significant finding in this study is the calculated risk of SO development after a single VR procedure, which was significantly lower in our cohort than that previously reported in the literature. This was seen to rise exponentially with additional procedures.