Objective
Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by mutations in the gene encoding for the mitochondrial protein frataxin, is characterized by ataxia and ...gait instability, immobility, and eventual death. We evaluated corneal confocal microscopy (CCM) quantification of corneal nerve morphology as a novel, noninvasive, in vivo quantitative imaging biomarker for the severity of neurological manifestations in FRDA.
Methods
Corneal nerve fiber density, branch density, and fiber length were quantified in individuals with FRDA (n = 23) and healthy age‐matched controls (n = 14). All individuals underwent genetic testing and a detailed neurological assessment with the Scale for the Assessment and Rating of Ataxia (SARA) and Friedreich's Ataxia Rating Scale (FARS). A subset of individuals with FRDA who were ambulatory underwent quantitative gait assessment.
Results
CCM demonstrated a significant reduction in nerve fiber density and length in FRDA compared to healthy controls. Importantly, CCM parameters correlated with genotype, SARA and FARS neurological scales, and linear regression modeling of CCM nerve parameter–generated equations that predict the neurologic severity of FRDA.
Interpretation
Together, the data suggest that CCM quantification of corneal nerve morphology is a rapid, sensitive imaging biomarker for quantifying the severity of neurologic disease in individuals with FRDA. Ann Neurol 2018;84:893–904
This study was designed with an aim to share our experience of primary pelvic exenterations. The study included 23 patients with different types of pelvic cancer enrolled at a single institution ...between November 2011 and July 2020. The patient mean age was 55 years (range, 43-72 years) and the oncological indications included: Stage IVa cervical cancer (11 cases, 48.9%), stage IVa endometrial cancer (1 case, 4.3%), stage IVa vaginal cancer (6 cases, 26%), stage IIIb bladder cancer (3 cases, 13%), stage IIIc rectal cancer (1 case, 4.3%) and undifferentiated pelvic sarcoma (1 case, 4.3%). Total, anterior, and posterior pelvic exenterations were performed on 34.4, 56.5 and 13% of cases, respectively. Related to levator ani muscle, 13 (56.5%) pelvic exenterations were supralevatorian, 10 (43.5%) infralevatorian, and 5 (21.7%) were infralevatorian with vulvectomy. No major intraoperative complications occurred. Seven patients (30.5%) developed early complications, 4 of them (17.4%) required reoperation and 1 (4.3%) perioperative death caused by a pulmonary embolism was recorded. Only 1 patient experienced a late complication, a urostomy stenosis. Over a median follow-up period of 35 months, 8 (34.8%) patients died. The median overall survival (OS) was 33 months (range, 1-96 months). The 2-year and 5-year survival rates were 72 and 66%, respectively. Primary pelvic exenteration may be related with various postoperative complications, without high perioperative morality and with long-term survival.
Inhibition of vascular endothelial growth factor (VEGF) for the management of the pathological ocular neovascularization associated with diseases such as neovascular age-related macular degeneration ...is a proven paradigm; however, monthly intravitreal injections are required for optimal treatment. We have previously shown that a novel, secreted anti-VEGF molecule sFLT01 delivered by intravitreal injection of an AAV2 vector (AAV2-sFLT01) gives persistent expression and is efficacious in a murine model of retinal neovascularization. In the present study, we investigate transduction and efficacy of an intravitreally administered AAV2-sFLT01 in a nonhuman primate (NHP) model of choroidal neovascularization (CNV). A dose-dependent and persistent expression of sFLT01 was observed by collecting samples of aqueous humor at different time points over 5 months. The location of transduction as elucidated by in situ hybridization was in the transitional epithelial cells of the pars plana and in retinal ganglion cells. AAV2-sFLT01 was able to effectively inhibit laser-induced CNV in a dose-dependent manner as determined by comparing the number of leaking CNV lesions in the treated versus control eyes using fluorescein angiography. Our data suggest that intravitreal delivery of AAV2-sFLT01 may be an effective long-term treatment for diseases caused by ocular neovascularization.
Carcinosarcoma, also known as malignant mixed Mullerian tumor (MMMT), includes both malignant epithelial and mesenchymal elements. While the endometrium is the most frequent known site for ...carcinosarcomas, their development in the fallopian tube is rare condition, only accounting for 0.1 to 0.5% among all gynecological malignancies. Fallopian tube MMMT is associated with an aggressive progression. A total of 94 previous case reports were reviewed and divided, after applying the exclusion criteria, into 2 groups: No evidence of disease (NED) Group including 33 patients reported to be without any residual disease at the end of the follow-up period; death of disease (DOD) Group including 51 patients who died due to the progression of fallopian carcinosarcoma or its complications. The gathered data were statistically analyzed together with a case from our clinical experience: a 65-year-old postmenopausal patient with a final histological diagnosis of fallopian carcinosarcoma staged FIGO IC2, synchronous with a serous endometrial intraepithelial carcinoma. Patient age between 41 and 60 years, symptoms at presentation and computed tomography (CT)/magnetic resonance imaging (MRI) tumor evidence are prognostic factors (P<0.05). Omentectomy odds ratio (OR)=0.3545 and pelvic lymphadenectomy (OR=0.3732) were found to be significant factors for survival (P<0.05). Fimbrial localization of the tumor is a negative prognosis factor (OR=4.263), as well as the heterologous type of tumor (OR=2.880). Chemotherapy was found to improve survival (OR=0.2679) while radiotherapy had no influence on patient prognosis. Reporting these rare cases could be essential for obtaining more precise information regarding the treatment and prognosis of patients with MMMT of the fallopian tube, in order to improve patient survival and quality of life. Key words: fallopian tube, carcinosarcoma, surgery, chemotherapy, omentectomy, lymphadenectomy
The aim of this study was to present our experience of 18 cases of abdominal radical trachelectomy (ART), including 5 performed during pregnancy, analyzing patient selection, surgical complications, ...and oncological and obstetrical outcomes. This reproductive study included all early stage cervical cancer patients referred for ART at the 1st Obstetrics and Gynecology Clinic of the Emergency Clinical County Hospital Targu Mures, between 2010 and 2020. A total of 19 women were considered for ART, and only 1 case required conversion to radical hysterectomy. The patient mean age was 31 years (range 24-38 years), and 66.67% of the patients were nulliparous. Six women (33.33%) had stage IA2, 4 (22.22%) had stage IB1, 5 (27.78%) had stage IB2, and 4 (22.22%) had stage IB3 disease. One intraoperative complication occurred in this series, which consisted in both right ureteral and bladder injuries. Early postoperative complications were represented by urinary bladder dysfunction (33.33%), symptomatic pelvic lymphocele (11.1%), peritonitis (5.5%), and wound infection (5.5%). Late postoperative complications included cervical stenosis (5.5%), amenorrhea (11.1%), and pelvic abscess (5.5%). Four out of the 18 patients were operated on during pregnancy between 14 and 20 weeks; 2 of them gave birth at term, 2 of them aborted shortly after the surgery. Two vaginal recurrences were recorded; both were managed by hysterectomy, partial colpectomy and adjuvant chemoradiotherapy. At this moment, all patients are alive with no evidence of disease and 3 of them managed to conceive. In conclusion, ART should be recommended as a fertility-preserving procedure for women in their reproductive age. In selected cases, ART can be performed during pregnancy with encouraging results.
Abstract Purpose To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome. Design Post-hoc analysis of ...randomized-controlled-trial data Methods Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network’s Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52‒156) visual acuity response mean change from baseline in best-corrected visual acuity (CFB BCVA); categorized improvement (<5, 5‒9, or ≥10 Early Treatment Diabetic Retinopathy Study ETDRS letters) in BCVA. Results In the analysis population (340 eyes), <5, 5‒9, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2% and 37.1% of eyes, respectively, at 12 weeks, and 34.2%, 16.5% and 49.3% of eyes at 156 weeks. Within each early BCVA response category (<5, 5‒9, and ≥10 letter- improvement at 12 weeks), mean CFB BCVA at 52‒156 weeks varied by <5 letters from that at 12 weeks. CFB BCVA and <5-letter improvement at 12 weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156 weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders. Conclusions Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks).
To evaluate patients with diabetic retinopathy using ultra-wide-field fluorescein angiography and to compare the visualized retinal pathology with that seen on an overly of conventional 7 standard ...field (7SF) imaging.
Two hundred and eighteen eyes of 118 diabetic patients who underwent diagnostic fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. The visualized area of the retina, retinal nonperfusion, retinal neovascularization, and panretinal photocoagulation were quantified by two independent masked graders. The respective areas identified on the ultra-wide-field fluorescein angiography image were compared with an overly of a modified 7SF image as outlined in the Early Treatment Diabetic Retinopathy Study.
Ultra-wide-field fluorescein angiograms imaging, on average, demonstrated 3.2 times more total retinal surface area than 7SF. When compared with 7SF, ultra-wide-field fluorescein angiography showed 3.9 times more nonperfusion (P < 0.001), 1.9 times more neovascularization (P = 0.036), and 3.8 times more panretinal photocoagulation (P < 0.001). In 22 eyes (10%), ultra-wide-field fluorescein angiography demonstrated retinal pathology (including nonperfusion and neovascularization) not evident in an 7SF overly.
Compared with conventional 7SF imaging, ultra-wide-field fluorescein angiography reveals significantly more retinal vascular pathology in patients with diabetic retinopathy. Improved retinal visualization may alter the classification of diabetic retinopathy and may therefore influence follow-up and treatment of these patients.
The authors report a case series of five women with the diagnosis of polycystic ovary syndrome (PCOS) (n = 4) or a first-degree relative with PCOS (n = 1) who presented with central serous ...chorioretinopathy (CSR). This report is the first to correlate PCOS and CSR on clinical presentation. Patients with PCOS often exhibit physical evidence of elevated androgens, such as testosterone, which recently has been linked to CSR. The authors suggest that women with CSR be investigated for PCOS if indicated clinically. In addition, further studies should investigate the relationship between the two disorders.
Wide-field Imaging of the Retina Witmer, Matthew T., MD; Kiss, Szilárd, MD
Survey of ophthalmology,
03/2013, Letnik:
58, Številka:
2
Journal Article
Recenzirano
Abstract The retinal periphery is the site of pathology in several eye diseases. Imaging of the peripheral retina offers a way to diagnose, monitor, and evaluate responses to the treatment of these ...conditions. Traditional fundus cameras have offered a 30- to 50-degree field of view. Recent technology has advanced to provide up to a 200-degree field of view. The utility of this technology in clinical practice continues to be investigated; wide-field color photography, autofluorescence imaging, and fluorescein angiography have been used for imaging peripheral retinal disease. Due to the limitations of this imaging technology and the lack of normative data, however, the clinical role of wide-field imaging remains controversial.
To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in ...United States clinical practice.
Retrospective observational cohort study.
Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016.
Analysis of longitudinal electronic health records from USRetina.
Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent.
Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 μm (mean change, -48 μm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters.
This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice.
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