Ada Orrico

Automatic prediction of cardiovascular and cerebrovascular events using heart rate variability analysis.

Background There is consensus that Heart Rate Variability is associated with the risk of vascular events. However, Heart Rate Variability predictive value for vascular events is not completely clear. The aim of this study is to develop novel predictive models based on data-mining algorithms to provide an automatic risk stratification tool for hypertensive patients. Methods A database of 139 Holter recordings with clinical data of hypertensive patients followed up for at least 12 months were collected ad hoc. Subjects who experienced a vascular event (i.e., myocardial infarction, stroke, syncopal event) were considered as high-risk subjects. Several data-mining algorithms (such as support vector machine, tree-based classifier, artificial neural network) were used to develop automatic classifiers and their accuracy was tested by assessing the receiver-operator characteristics curve. Moreover, we tested the echographic parameters, which have been showed as powerful predictors of future vascular events. Results The best predictive model was based on random forest and enabled to identify high-risk hypertensive patients with sensitivity and specificity rates of 71.4% and 87.8%, respectively. The Heart Rate Variability based classifier showed higher predictive values than the conventional echographic parameters, which are considered as significant cardiovascular risk factors. Conclusions Combination of Heart Rate Variability measures, analyzed with data-mining algorithm, could be a reliable tool for identifying hypertensive patients at high risk to develop future vascular events.

Macular Function and Morphologic Features in Juvenile Stargardt Disease: Longitudinal Study

PURPOSE To evaluate disease progression in a cohort of patients with a clinical and genetic diagnosis of Stargardt disease. DESIGN Longitudinal cohort study. PARTICIPANTS A total of 56 selected patients with a clinical and molecular diagnosis of Stargardt disease, an early age of onset, and a median follow-up length of 2 years. METHODS Patients underwent routine examination, including full-field electroretinography, microperimetry, and optical coherence tomography. MAIN OUTCOME MEASURES Best-corrected visual acuity (BCVA), mean retinal sensitivity, fixation stability, preferred retinal locus, inner segment/outer segment (IS/OS) junction loss, and atrophic lesion area. RESULTS A total of 56 patients with a mean age at disease onset of 15.3 years (range, 3-28 years), a mean disease duration of 12.1 years, and a mean age at baseline of 27.4 years were analyzed. The median BCVA was 20/200 in both eyes. Optical coherence tomography parameters (IS/OS alteration and retinal pigment epithelium lesion area) were obtained in only 49 patients because the signal quality was poor in the remaining 7 patients. Optical coherence tomography revealed a mean retinal pigment epithelium lesion area of 2.6 mm(2), preserved foveal IS/OS in 4.1% of patients, loss of foveal IS/OS in 59.2% of patients, and extensive loss of macular IS/OS in 36.7% of patients. Microperimetric findings showed a reduced macular sensitivity (mean, 10 decibels [dB]) and an unstable fixation in half of the patient cohort. The longitudinal analysis showed a significant progressive reduction of BCVA and macular sensitivity (at an estimated rate of 0.04 decimals and 1.19 dB/year, respectively) associated with a significant enlargement of retinal pigment epithelium lesion area (0.282 mm(2)/year). No significant changes in ophthalmoscopic findings and electroretinographic responses were detected. CONCLUSIONS This study highlights the importance of microperimetry and optical coherence tomography in monitoring patients with Stargardt disease. Quantifying the decline of visual functionality and detecting morphologic macular changes prove useful in evaluating disease progression over a short-term follow-up and should be taken into account for the design of future clinical trials of gene therapy to treat retinal dystrophy.

Standard versus trans-epithelial collagen cross-linking in keratoconus patients suitable for standard collagen cross-linking.

Purpose Evaluating the clinical results of trans-epithelial collagen cross-linking (CXL) and standard CXL in patients with progressive keratoconus. Methods This prospective study comprised 20 eyes of 20 patients with progressive keratoconus. Ten eyes were treated by standard CXL and ten by trans-epithelial cross-linking (TE-CXL, epithelium on) with 1 year of follow-up. All patients underwent complete ophthalmologic testing that included pre- and postoperative uncorrected visual acuity, corrected visual acuity, spherical error, spherical equivalent, corneal astigmatism, simulated maximum, minimum, and average keratometry, coma and spherical aberration, optical pachymetry, and endothelial cell density. Intra-and postoperative complications were recorded. The solution used for standard CXL comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), while the solution for TE-CXL (Ricrolin, TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with UV-X System at 3 mW/cm2. Results In both the standard CXL group (ten patients, ten eyes; mean age, 30.4±7.3 years) and the TE-CXL group (ten patients, ten eyes; mean age, 28±3.8 years), uncorrected visual acuity and corrected visual acuity improved significantly after treatment. Furthermore, a significant improvement in topographic outcomes, spherical error, and spherical equivalent was observed in both groups at month 12 posttreatment. No significant variations were recorded in other parameters. No complications were noted. Conclusion A 1-year follow-up showed stability of clinical and refractive outcomes after standard CXL and TE-CXL.

A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2.

BackgroundWolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2.Case presentationThe proband was a 17 year-old girl. She presented diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion of CISD2 in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation. Long runs of homozygosity analysis from SNP-array data did not show any degree of parental relationship, but the microsatellite analysis confirmed the hypothesis of a common ancestor.ConclusionOur patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the “asymptomatic” optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS. In addition, we found an impaired aggregation to ADP and not to collagen as previously reported, thus it is possible that different experimental conditions or inter-patient variability can explain different results in platelet aggregation. Further clinical reports are necessary to better define the clinical spectrum of this syndrome and to re-evaluate its classification.

A pilot study for development of a novel tool for clinical decision making to identify fallers among ophthalmic patients

BackgroundFalls in the elderly is a major problem. Although falls have a multifactorial etiology, a commonly cited cause of falls in older people is poor vision. This study proposes a method to discriminate fallers and non-fallers among ophthalmic patients, based on data-mining algorithms applied to health and socio-demographic information.MethodsA group of 150 subjects aged 55 years and older, recruited at the Eye Clinic of the Second University of Naples, underwent a baseline ophthalmic examination and a standardized questionnaire, including lifestyles, general health, social engagement and eyesight problems. A subject who reported at least one fall within one year was considered as faller, otherwise as non-faller. Different tree-based data-mining algorithms (i.e., C4.5, Adaboost and Random Forest) were used to develop automatic classifiers and their performances were evaluated by assessing the receiver-operator characteristics curve estimated with the 10-fold-crossvalidation approach.ResultsThe best predictive model, based on Random Forest, enabled to identify fallers with a sensitivity and specificity rate of 72.6% and 77.9%, respectively. The most informative variables were: intraocular pressure, best corrected visual acuity and the answers to the total difficulty score of the Activities of Daily Vision Scale (a questionnaire for the measurement of visual disability).ConclusionsThe current study confirmed that some ophthalmic features (i.e. cataract surgery, lower intraocular pressure values) could be associated with a lower fall risk among visually impaired subjects. Finally, automatic analysis of a combination of visual function parameters (either self-evaluated either by ophthalmological test) and other health information, by data-mining algorithms, could be a feasible tool for identifying fallers among ophthalmic patients.

Subretinal Fibrosis in Stargardt's Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation

Purpose: To report on 4 patients affected by Stargardt’s disease (STGD) with fundus flavimaculatus (FFM) and ABCA4 gene mutation associated with subretinal fibrosis. Methods: Four patients with a diagnosis of STGD were clinically examined. All 4 cases underwent a full ophthalmologic evaluation, including best-corrected visual acuity measured by the Snellen visual chart, biomicroscopic examination, fundus examination, fundus photography, electroretinogram, microperimetry, optical coherence tomography and fundus autofluorescence. All patients were subsequently screened for ABCA4 gene mutations, identified by microarray genotyping and confirmed by conventional DNA sequencing of the relevant exons. Results: In all 4 patients, ophthalmologic exam showed areas of subretinal fibrosis in different retinal sectors. In only 1 case, these lesions were correlated to an ocular trauma as confirmed by biomicroscopic examination of the anterior segment that showed a nuclear cataract dislocated to the superior site and vitreous opacities along the lens capsule. The other patients reported a lifestyle characterized by competitive sport activities. The performed instrumental diagnostic investigations confirmed the diagnosis of STGD with FFM in all patients. Moreover, in all 4 affected individuals, mutations in the ABCA4 gene were found. Conclusions: Patients with the diagnosis of STGD associated with FFM can show atypical fundus findings. We report on 4 patients affected by STGD with ABCA4 gene mutation associated with subretinal fibrosis. Our findings suggest that this phenomenon can be accelerated by ocular trauma and also by ocular microtrauma caused by sport activities, highlighting that lifestyle can play a role in the onset of these lesions.

Wearable technology and ECG processing for fall risk assessment, prevention and detection

Falls represent one of the most common causes of injury-related morbidity and mortality in later life. Subjects with cardiovascular disorders (e.g., related to autonomic dysfunctions and postural hypotension) are at higher risk of falling. Autonomic dysfunctions increasing the risk of falling in the short and mid-term could be assessed by Heart Rate Variability (HRV) extracted by electrocardiograph (ECG). We developed three trials for assessing the usefulness of ECG monitoring using wearable devices for: risk assessment of falling in the next few weeks; prevention of imminent falls due to standing hypotension; and fall detection. Statistical and data-mining methods are adopted to develop classification and regression models, validated with the cross-validation approach. The first classifier based on HRV features enabled to identify future fallers among hypertensive patients with an accuracy of 72% (sensitivity: 51.1%, specificity: 80.2%). The regression model to predict falls due to orthostatic dropdown from HRV recorded before standing achieved an overall accuracy of 80% (sensitivity: 92%, specificity: 90%). Finally, the classifier to detect simulated falls using ECG achieved an accuracy of 77.3% (sensitivity: 81.8%, specificity: 72.7%). The evidence from these three studies showed that ECG monitoring and processing could achieve satisfactory performances compared to other system for risk assessment, fall prevention and detection. This is interesting as differently from other technologies actually employed to prevent falls, ECG is recommended for many other pathologies of later life and is more accepted by senior citizens.

En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease.

Purpose We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). Methods We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. Results The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P < 0.001). Moreover, the longitudinal analysis, performed in 98 patients, showed a significant enlargement of macular lesion area at an estimated exponential rate of 4.6% per year (P = 0.046), together with a significant worsening of BCVA (0.06 logMAR per year; P < 0.001) and a significant decrease of macular thickness (1.6% per year; P = 0.005) over the follow-up. Conclusions The current study describes, for the first time in literature, a longitudinal analysis of the macular lesion area assessed by SD-OCT in STGD1 disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials.

Functional improvement assessed by multifocal electroretinogram after Ocriplasmin treatment for vitreomacular traction

BackgroundTo evaluate the functional recovery of patients with symptomatic vitreomacular traction (VMT) after Ocriplasmin treatment.MethodsProspective, single centre, consecutive case series. Patients were treated with a single intravitreal injection of Ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis EU). The following outcome measures are considered: resolution of VMT, evaluated through the use of optical coherence tomography (SD-OCT), functional recovery evidenced by multifocal-electroretinogram (mfERG) and microperimetry (MP1) after treatment with Ocriplasmin.ResultsFour eyes of four patients were treated with Ocriplasmin injection. We observed a VMT non-surgical resolution in all patients. The longitudinal statistical analysis showed a significant improvement of best corrected visual acuity (BCVA) in the treated eye of about 0.97 letters/week (p = 0.033). No significant difference was observed in mean sensitivity (p > 0.05) assessed by MP1 in both eyes, while improvement in fixation stability was assessed in treated eyes (β = 0.39; p = 0.029). In the four treated eyes mfERG revealed an increased foveal peak response over the follow-up. The longitudinal analysis of mfERG data shows a significant increase of N1 and P1 amplitude in the first rings and a significant decrease of N1 and P1 implicit time in most rings.ConclusionsWe report on four cases with resolution of VMT after Ocriplasmin treatment. Our preliminary results demonstrate that Ocriplasmin is safe and effective in the treatment of VMT, because it not only leads to a morphological recovery but mostly to a restoration of macular functionality, evaluated through the use of different objective tests, such as MP1 and mfERG over a six-month follow-up.

Photorefractive Keratectomy on Purely Refractive Accommodative Esotropia

Abstract Context: Results on refractive keratectomy of the treatment of young patients with purely refractive accommodative esotropia. Aims: Evaluating the results of refractive keratectomy (PRK) on the treatment of young patients with purely refractive accommodative esotropia. Methods and Material: This prospective study comprised patients with purely accommodative hyperopic esotropia. Patients underwent a complete ophthalmologic examination that included pre-operative and post-operative best corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA) (at 3, 12, and 24 months), alignment and sensory outcomes; keratometry, pachymetry, and corneal topography. Statistical analysis used: paired T-student. Results: Twenty eyes of 10 patients (mean age 21.5 years) were treated. The pre-operative mean UCVA was 0.70 logMAR (SD ± 0.177) and 0.02 logMAR (SD ± 0.029) two years later. The pre-operative BCVA was 0.02 logMAR (SD ± 0.037) and 0.01 (SD ± 0.026) two years later. The mean spherical equivalent (SE) in cyclopegia was + 3.92 D (range: +2.75 to +5.00 D; SD = 0.62) pre-operatively, −0.69 D (range −0.5 to −1) at three months and 0 D (range: −0.25 to 0.25) at one and two years later. After surgery, all patients were orthophoric without correction and stereopsis was unaffected by PRK. Conclusions: A two-year follow-up showed that photorefractive keratectomy was an effective treatment for esotropia associated with mild to moderate hyperopia in young adults with purely refractive accommodative esotropia.