Deep Anterior Lamellar Keratoplasty Using Dehydrated versus Standard Organ Culture-Stored Donor Corneas: Prospective Randomized Trial.

PURPOSE: To compare the outcomes of deep anterior lamellar keratoplasty (DALK) using dehydrated versus standard organ culture-stored donor corneas for eyes with keratoconus. DESIGN: Prospective, randomized, single-center trial conducted in Italy. PARTICIPANTS: Adult patients (age ≥ 18 years) with keratoconus scheduled for elective DALK. METHODS: Patients undergoing successful type 1 bubble pneumatic dissection using a standard DALK technique were randomized during surgery to receive either dehydrated (n = 30) or standard organ culture-stored (n = 30) donor corneas. MAIN OUTCOME MEASURES: The primary study outcome was best spectacle-corrected visual acuity (BSCVA) 12 months after surgery. Secondary outcomes were refractive astigmatism (RA), endothelial cell density (ECD), and complication rates. RESULTS: Postoperative BSCVA did not significantly differ between groups at both time points: mean difference at 6 months was 0.030 logarithm of the minimum angle of resolution (logMAR; 95% confidence interval [CI], -0.53 to 0.10 logMAR; P = 0.471) and at 12 months was -0.013 logMAR (95% CI, -0.10 to 0.08 logMAR; P = 0.764). No significant differences between groups were observed in terms of postoperative RA and ECD at all time points. In the first 3 days after DALK, an epithelial defect was present in 10 patients (33%) in the organ culture cornea group and in 29 patients (97%) in the dehydrated cornea group. Complete re-epithelialization was achieved by day 7 in all patients (100%) in both groups. CONCLUSIONS: The study provides evidence that the use of dehydrated corneas is noninferior to the use of standard organ culture donor corneas for DALK. Corneal tissue dehydration represents a viable solution that can allow long-term cornea preservation and avoid wastage of unused corneas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

STELLATE MULTIFORM AMELANOTIC CHOROIDOPATHY: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSION: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."

Discharge Monitoring in Open-Channels: An Operational Rating Curve Management Tool.

An aspect correlated with climate change is certainly represented by the alternation of severe floods and relevant drought periods. Moreover, there is evidence that changes in climate and land cover are inducing changes in stream channel cross-sections, altering local channel capacity. A direct consequence of a significant change in the local channel capacity is that the relationship between the amount of water flowing at a given point in a river or stream (usually at gauging stations) and the corresponding stage in that section, known as a stage-discharge relationship or rating curve, is changed. The key messages deriving from the present work are: (a) the more frequent and extreme the floods become, the more rapid the changes in the stream channel cross-section become, (b) from an operational point of view, the collection and processing of field measurements of the stage and corresponding discharge at a given section in order to quickly and frequently update the rating curve becomes a priority. It is, therefore, necessary to define a control system for acquiring hydrological data capable of keeping river levels and discharges under control to support flood early warnings and water management. The proposed stage-discharge management system is used by the Civil Protection Service of the Marche Region (east-central Italy) for the monitoring of river runoff in the regional watersheds. The Civil Protection Service staff performs stage-discharge field measurements using water level sensors and recorders (e.g., staff gauges, submersible pressure transducers, ultrasound and radar sensors) and a current meter, acoustic doppler velocimeter, acoustic doppler current profilers, portable mobile radar profiler and salt dilution method equipment, respectively. Power functions are fitted to the stage-discharge field data. Furthermore, extrapolation is performed to cover the full range of flow measurements; in general, extrapolation is not an easy task because of sharp changes in the stream cross-section geometry for very high or very low stages. In the present work, we also focused attention on the application problems that occur in practice and the need for frequent updating.

Contrast-Enhanced Mammography Versus MRI in the Evaluation of Neoadjuvant Therapy Response in Patients With Breast Cancer: A Prospective Study.

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM (p = .001) and delayed CEM (p = .002); remaining comparisons were not significant (p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

DOUBLE FLUENCE PHOTODYNAMIC THERAPY FOR THE TREATMENT OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To evaluate the efficacy and safety of double-fluence photodynamic therapy for the treatment of circumscribed choroidal hemangioma. METHODS: Retrospective observational study including patients affected by circumscribed choroidal hemangioma and treated with double-fluence photodynamic therapy. The photodynamic therapy was performed with verteporfin infusion intravenously (dose of 6 mg/m2 body surface area over 10 minutes), followed by the application of two consecutive spots of 50 J/cm2 light at 689 nm for 83 seconds. RESULTS: Twenty-three eyes of 23 patients were included. The mean best-corrected visual acuity increased from 20/45 to 20/28, the mean tumor thickness decreased from 2,758 ± 530 µm to 722 ± 314 µm (P < 0.05), and the mean central retinal thickness decreased from 404 ± 209 µm to 188 ± 56 µm (P < 0.05) in 12 months, respectively. A total reabsorption of macular subretinal fluid, cystoid macular edema, and SRF associated with the tumor was obtained within 6 months in all cases, with persistence of tumor-associated intraretinal fluid up to 12 months only in two patients. No cases of side effects or need for retreatment were reported during the follow-up (average time of 25 months). CONCLUSION: Double-fluence photodynamic therapy is a safe and effective treatment for circumscribed choroidal hemangiomas and should be considered as the first line of treatment for these lesions.

Outcomes of serial sessions of Activa mask combined with intense pulsed light therapy in patients with Meibomian gland dysfunction.

BACKGROUND: To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). METHODS: Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire. RESULTS: Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 µm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH. CONCLUSIONS: Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients.

Accuracy of intraocular lens power calculation for cataract surgery after deep anterior lamellar keratoplasty.

BACKGROUND: The purpose of this study was to assess the accuracy of intraocular lens power (IOL) formulas for cataract surgery after deep anterior lamellar keratoplasty (DALK). METHODS: This retrospective study included eyes which had previously undergone DALK and underwent standard phacoemulsification with monofocal IOL implantation between January 2012 and January 2021 at Ospedali Privati Forlì "Villa Igea" (Forlì, Italy). The predicted spherical equivalent (SE) was calculated using the Barrett Universal II, Emmetropia Verifying Optical (EVO), Haigis, Hoffer Q, Hoffer QST, Holladay 1, Holladay II, Kane and SRK/T formulas. Prediction error (PE) was calculated as the actual postoperative SE refraction minus the SE predicted refraction. RESULTS: Eighty-two eyes of 82 patients were included. The mean PE was negative using all formulas. Friedman test revealed a statistically significant difference of the median absolute PE (MedAE) among the different IOL formulas (P = 0.005). On the basis of the MedAE, the formulas were ranked as follows: SRK/T (0.805 D), Kane (0.810 D), EVO (0.845 D), Hoffer QST (0.847 D), Barrett (0.895 D), Holladay 1 (0.915 D), Haigis (1.010 D) and Hoffer Q (1.070 D) formulas. CONCLUSIONS: All formulas had a tendency towards a myopic refractive shift in post-DALK eyes. Although the SRK/T, Kane, EVO and Hoffer QST formulas were more accurate, predictability of refractive outcomes was lower than in virgin eyes.

Experimental testing of air filter efficiency against the SARS-CoV-2 virus: The role of droplet and airborne transmission.

Verifying the capacity of different types of air filters to stop the propagation of the SARS-CoV-2 virus has become a strategic element to contain viral spreading in enclosed spaces. This paper shows the results of experimental tests about the capacity of different commercial filter grades to stop SARS-CoV-2 propagation using inactivated virions. In the first test, the obtained results showed that the F8 filter blocks SARS-CoV-2 propagation if it encounters a flow devoid of liquid phase, i.e., a biphasic flow that can wet the filtering material. On the contrary, as shown in the second test, the SARS-CoV-2 virus propagates through the F8 filter if the droplet content in the air flow is enough to wet it. In these operational conditions, i.e., when the filter is wet by a flow with a high droplet content, the absolute H14 filter was also shown to fail to stop the transmission of the SARS-CoV-2 virus. Lastly, in the third test, the viral load was shown to be stopped when the pathway of the infected droplet is blocked.

Retinal microcirculation abnormalities in patients with systemic sclerosis: an explorative optical coherence tomography angiography study.

OBJECTIVES: To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). METHODS: A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. RESULTS: The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. CONCLUSION: We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.

miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts cardiac development and electrical activity in zebrafish.

To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5lox/+and Tbx5del/+ mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. MiR-182-5p, the most highly expressed miRNA of this family, was functionally analyzed in zebrafish. Transient overexpression of miR-182-5p affected heart morphology, calcium handling and the onset of arrhythmias as detected by ECG tracings. Accordingly, several calcium channel proteins identified as putative miR-182-5p targets were downregulated in miR-182-5p overexpressing hearts. In stable zebrafish transgenic lines, we demonstrated that selective miRNA-182-5p upregulation contributes to arrhythmias. Moreover, cardiac-specific down-regulation of miR-182-5p rescued cardiac defects in a zebrafish model of Holt-Oram syndrome. In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development.

Automated digital analysis of intraoperative keratoscopy and its correlation with postoperative astigmatism after big-bubble deep anterior lamellar keratoplasty.

PURPOSE: To investigate the correlation between postoperative corneal astigmatism (PCA) and values of intraoperative keratoscopy analyzed with a newly developed automated technique in patients undergoing big-bubble (BB) deep anterior lamellar keratoplasty (DALK). METHODS: Photographs of keratoscope rings taken at the end of BB-DALK were analyzed using ImageJ for the calculation of "roundness" (R): values = 1 indicate a perfect circle. Pearson's correlation was used to evaluate the relationship between R and PCA that measured 1 week (V1), 3 months (V2), and 18 months (V3), postoperatively. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the accuracy of R for identifying patients with PCA < 3 diopters (D). The point on the ROC curve nearest to the coordinate (0,100) was used as a cutoff to determine sensitivity and specificity. RESULTS: Data from 121 patients were included. The mean value of R*was 0.93 ± 0.04 (range 0.76-0.99). R showed a significant correlation with PA at V3 (R = - 0.42, P < 0.01). The ROC curve had an AUC of 0.69 (95% CI 0.59-0.79). A cutoff value of R = 0.93 had a sensitivity of 70.3% and specificity of 61.0% for identifying patients with PA < 3D at V3. CONCLUSIONS: This new digital analysis of keratoscope rings allows to identify with reasonably good diagnostic accuracy patients with low values of post-DALK astigmatism correctable with spectacles.

Short-term choroidal vascular changes after aflibercept therapy for neovascular age-related macular degeneration.

INTRODUCTION: The purpose of this study was to evaluate choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept injection over a 3-month period. METHODS: Enhanced depth imaging optical coherence tomography scans of 60 eyes with treatment-naïve nAMD and 60 unaffected fellow eyes were retrospectively analyzed. Data was collected at baseline and after 3 monthly intravitreal injections of aflibercept. The ImageJ software was used to binarize OCT scans and measure total choroid area (TCA), luminal area (LA), and stromal area (SA). Choroidal vascularity index (CVI) was defined as the ratio of LA to TCA. RESULTS: After treatment, subfoveal choroidal thickness (CT) in nAMD eyes significantly decreased from 210. 6 ± 61.6 to 194.6 ± 58.7 µm (P < 0.001), TCA from 1.620 ± 0.502 to 1.500 ± 0.451 mm2 (P < 0.001), LA from 1.075 ± 0.335 to 0.985 ± 0.307 mm2 (P < 0.001), SA from 0.545 ± 0.176 to 0.516 ± 0.153 mm2 (P = 0.005), and CVI from 66.36 ± 2.89 to 65.46 ± 2.87% (P = 0.009). The decrease of CVI after treatment was significantly correlated with baseline CVI (Rs = 0.466, P < 0.001), but not with the change in BCVA and presence of dry macula after treatment (always P > 0.05). CONCLUSION: Choroidal thickness and vascularity significantly decreased after treatment with aflibercept in nAMD eyes. Besides the pharmacologic effect on the neovascular lesion, aflibercept may induce vascular changes also on the underlying choroid.

EXTENDED FIELD IMAGING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FOR THE STUDY OF RETINAL AND CHOROIDAL CHANGES AFTER RADIATION THERAPY FOR CHOROIDAL MELANOMA: Comparison With Wide-Field Angiography.

PURPOSE: Radiation retinopathy is a common side effect of ocular radiotherapy with no long-term effective therapy. Optical coherence tomography angiography (OCTA) and wide-field fluorescein angiography (FA) are widely used for the study of radiation maculopathy and peripheral nonperfusion, respectively. We investigated the role of extended field imaging (EFI-OCTA) for the study of retinal and choroidal alterations after radiotherapy for choroidal melanoma. METHODS: Cross-sectional observational study of 20 eyes of 20 patients diagnosed with radiation retinopathy. All patients underwent a complete imaging evaluation including FA and indocyanine green angiography (ICGA) with 55° and 102° lens (Spectralis Heidelberg Engineering, Heidelberg, Germany). Optical coherence tomography angiography imaging was performed with the Zeiss PlexElite 9000 Swept Source OCTA (Carl Zeiss Meditec, Dublin, CA) using a 12 × 12-mm volume scan pattern centered on the fovea and a +20.00-diopter lens specifically designed to obtain EFI examination. The imaging methods were then compared in terms of visible field of view, extension of nonperfused areas, and vessel density. RESULTS: The mean extension ratio of EFI-OCTA compared to OCTA without EFI, FA/ICGA 55° and FA/ICGA 102° was, respectively, 1.98 ± 0.02, 1.21 ± 0.01 and 0.36 ± 0.003. The mean extension of retinal and choroidal nonperfused areas evaluated by EFI-OCTA (63.03 ± 48.21 and 38.63 ± 30.83 mm2) were significantly higher than with OCTA without EFI (40.40 ± 34.87 and 24.26 ± 21.82 mm2, P < 0.001) but lower than with FA/ICGA 102° (140.7 ± 69.23 and 108.3 ± 69.51 mm2, P < 0.001). No significant differences were found between mean extension of retinal and choroidal ischemic areas measured with EFI-OCTA and FA/ICGA 55° (69.64 ± 51.92 and 47.23 ± 33.59 mm2). The mean vessel density of EFI-OCTA (retina and choroid segmentation) was significantly different compared to OCTA without EFI (P < 0.05). Retinal vessel density was negatively correlated to retinal extension of nonperfused areas (r = -0.5, P = 0.02), and choroidal vessel density was negatively correlated to choroidal nonperfused areas (r = -0.6, P = 0.003) measured with EFI-OCTA. CONCLUSION: In our series, EFI-OCTA captured larger areas than OCTA without EFI and FA/ICGA with 55° lens. EFI-OCTA images showed a good definition of retinal and choroidal vascular changes after radiotherapy, suggesting a possible role of this safe and noninvasive imaging technique in the follow-up of patients with radiation retinopathy.

ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

PURPOSE: To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS: Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS: Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION: A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

Learning from organisational changes in the management of breast cancer patients during the COVID-19 pandemic: Preparing for a second wave at a breast unit in northern Italy.

Italy was the first western country to be hit by the initial wave of severe adult respiratory syndrome coronavirus 2 pandemic, which has been more widespread in the country's northern regions. Early reports showing that cancer patients are more susceptible to the infection posed a particular challenge that has guided our Breast Unit at Hub Hospital in Trento to making a number of stepwise operational changes. New internal guidelines and treatment selection criteria were drawn up by a virtual multidisciplinary tumour board that took into account the risks and benefits of treatment, and distinguished the patients requiring immediate treatment from those whose treatment could be delayed. A second wave of the pandemic is expected in the autumn as gatherings in closed places increase. We will take advantage of the gained experience and organisational changes implemented during the first wave in order to improve further, and continue to offer breast cancer management and treatment to our vulnerable patient population.

Dot2dot: accurate whole-genome tandem repeats discovery.

MOTIVATION: Large-scale sequencing projects have confirmed the hypothesis that eukaryotic DNA is rich in repetitions whose functional role needs to be elucidated. In particular, tandem repeats (TRs) (i.e. short, almost identical sequences that lie adjacent to each other) have been associated to many cellular processes and, indeed, are also involved in several genetic disorders. The need of comprehensive lists of TRs for association studies and the absence of a computational model able to capture their variability have revived research on discovery algorithms. RESULTS: Building upon the idea that sequence similarities can be easily displayed using graphical methods, we formalized the structure that TRs induce in dot-plot matrices where a sequence is compared with itself. Leveraging on the observation that a compact representation of these matrices can be built and searched in linear time, we developed Dot2dot: an accurate algorithm fast enough to be suitable for whole-genome discovery of TRs. Experiments on five manually curated collections of TRs have shown that Dot2dot is more accurate than other established methods, and completes the analysis of the biggest known reference genome in about one day on a standard PC. AVAILABILITY AND IMPLEMENTATION: Source code and datasets are freely available upon paper acceptance at the URL: https://github.com/Gege7177/Dot2dot. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS AFTER MYOPIC NEOVASCULARIZATION.

PURPOSE: To describe the optical coherence tomography (OCT) angiography features of subretinal fibrosis in eyes with myopic choroidal neovascularization after natural evolution or secondary to intravitreal anti-vascular endothelial growth factor therapy. METHODS: Retrospective observational case series. All eyes underwent a multimodal imaging examination including fluorescein angiography, spectral domain OCT, OCT angiography, and en face OCT. RESULTS: Twenty-five eyes of 25 patients with mean age of 56.4 ± 14.9 were included in the study. Subretinal fibrosis was diagnosed at mean 30 (range 6-116) months before inclusion. Within the subretinal fibrosis, an abnormal vascular network was observed in 20/25 (80%) eyes, located typically in the outer retina (18/20, 90%) or the choriocapillaris (14/20, 70%) segmentation. The most prevalent patterns were "round tangle" and "tapered tangle." On en face OCT, the subretinal fibrosis was evidenced in 24/25 (96%) eyes, most prevalently in the outer retina (21/25, 84%) and in the choriocapillaris (18/25, 72%), where main feature was white-hyperreflective (20/21, 95%) and dark-hyporeflective (17/18, 94%) appearance, respectively. The presence of subretinal fibrosis on en face OCT was positively correlated with the presence of abnormal vascular network on OCT angiography in 61% of the cases (P = 0.005). CONCLUSION: Subretinal fibrosis secondary to myopic choroidal neovascularization frequently contains blood flow within a persistent abnormal vascular network as assessed by OCT angiography.

CHOROIDAL VASCULARITY INDEX QUANTIFICATION IN GEOGRAPHIC ATROPHY USING BINARIZATION OF ENHANCED-DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHIC SCANS.

PURPOSE: To evaluate choroidal structural changes occurring over time in geographic atrophy (GA) secondary to age-related macular degeneration using choroidal vascularity index (CVI). METHODS: Enhanced-depth imaging optical coherence tomography scans of 34 patients with GA and 32 control subjects were retrospectively analyzed. Data were collected at baseline and after a mean follow-up of 18.3 ± 8.3 months. Choroidal images were binarized using the ImageJ software, and the luminal area and stromal area were segmented. Choroidal vascularity index was defined as the ratio of luminal area to total choroid area. RESULTS: Patients with GA showed significantly lower values of CVI, total choroid area, luminal area, and subfoveal choroidal thickness compared to control subjects (65.83 ± 3.95 vs. 69.33 ± 3.11, P < 0.001; 0.400 ± 0.239 mm vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 µm vs. 216.8 ± 58.8 µm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = -0.509; P = 0.002). During the follow-up period in patients with GA, subfoveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm to 0.156 ± 0.068 (P = 0.028), and CVI decreased from 65.83 ± 3.95 to 62.24 ± 3.63 (P < 0.001). CONCLUSION: This study showed for the first time that CVI is reduced in patients with GA, and that this metric further worsened during the follow-up period.

miRandola 2017: a curated knowledge base of non-invasive biomarkers.

miRandola (http://mirandola.iit.cnr.it/) is a database of extracellular non-coding RNAs (ncRNAs) that was initially published in 2012, foreseeing the relevance of ncRNAs as non-invasive biomarkers. An increasing amount of experimental evidence shows that ncRNAs are frequently dysregulated in diseases. Further, ncRNAs have been discovered in different extracellular forms, such as exosomes, which circulate in human body fluids. Thus, miRandola 2017 is an effort to update and collect the accumulating information on extracellular ncRNAs that is spread across scientific publications and different databases. Data are manually curated from 314 articles that describe miRNAs, long non-coding RNAs and circular RNAs. Fourteen organisms are now included in the database, and associations of ncRNAs with 25 drugs, 47 sample types and 197 diseases. miRandola also classifies extracellular RNAs based on their extracellular form: Argonaute2 protein, exosome, microvesicle, microparticle, membrane vesicle, high density lipoprotein and circulating. We also implemented a new web interface to improve the user experience.