Unilateral intraindividual comparison and bilateral performance of a monofocal spherical and diffractive extended depth of field intraocular lens mix-and-match approach.

BACKGROUND: To evaluate the intraindividual visual performance of a spherical and extended depth of field (EDOF) IOL used in a mix-and-match approach. METHODS: Single centre (tertiary care centre), retrospective consecutive case series. Included patients had uneventful cataract surgery with implantation of a spherical monofocal IOL (CT Spheris 204) in the dominant eye and a diffractive EDOF IOL (AT LARA 829) in the non-dominant eye. Monocular and binocular defocus curves and visual acuity at various distances were assessed. In addition, binocular reading speed, contrast sensitivity, and patient satisfaction using QOV, Catquest 9SF, and glare/halo questionnaires are reported. RESULTS: A total of 29 patients (58 eyes) were included. We observed significant intra-individual differences for monocular DCIVA, DCNVA, UIVA, and UNVA. There were no differences in monocular BCDVA or UDVA. The monocular defocus curves for the two IOLs significantly differed at defocus steps between -1.0 and -3.5 D. 93.10% of patients reported they would opt for the same combination of IOLs. CONCLUSION: Excellent uncorrected and corrected distance visual acuity was demonstrated in both groups. The mix-and-match approach described in this study yielded good intermediate vision and improved near vision with high-patient satisfaction.

Characteristics of surgically induced astigmatism after standardized microincisional cataract surgery with a superior limbal incision.

PURPOSE: To determine (1) if measurements of surgically induced astigmatism (SIA) as measured by keratometry (K) and total keratometry (TK) differ (2) if SIA affects the magnitude and/or meridian of keratometric astigmatism (3) if SIA evolves over time. SETTING: Tertiary care center. DESIGN: Retrospective data analysis. METHODS: A swept-source optical coherence tomography biometry dataset (IOLMaster700) consisting of 498 eyes (327 patients) from a tertiary care center was analyzed. For all eyes preoperative and postoperative biometric measurements at 1-month, 3-month, and 6-months postoperative visits were considered for vector analysis of SIA K and SIA TK . RESULTS: Centroids in right and left eyes were 0.26 diopters (D) @5 degrees/0.31 D @1 degree for SIA K and 0.27 D @4 degrees/0.34 D @1 degree for SIA TK . Centroids for difference vectors K-TK in right and left eyes were 0.02 D @ 176 degrees/0.03 D @6 degrees. The mean SIA magnitudes in right and left eyes were 0.48 ± 0.41 D and 0.50 ± 0.37 D for SIA K and 0.53 ± 0.42 D and 0.54 ± 0.40 D for SIA TK . In eyes with ATR astigmatism, an increase in postoperative astigmatism magnitude was more common than a decrease. More than 30% of eyes showed changes in the meridian of more than 15 degrees. CONCLUSIONS: Overall, we observed differences in K- and TK-derived SIA, and changes in SIA magnitude over time. For postsurgical interventions, postoperative astigmatism meridian values should be measured to base treatments. Astigmatism magnitude showed a tendency to decrease for steep-meridian incisions and to increase in flat-meridian incisions.

Update on Biometry and Lens Calculation - A Review of the Basic Principles and New Developments. / Update Biometrie und Linsenberechnung ­ ein Review zu Grundlagen und neuen Entwicklungen.

These days, accurate calculation of artificial lenses is an important aspect of patient management. In addition to the classic theoretical optical formulae there are a number of new approaches, most of which are available as online calculators. This review aims to explain the background of artificial lens calculation and provide an update on study results based on the latest calculation approaches. Today, optical biometry provides the computational basis for theoretical optical formulae, ray tracing, and also empirical approaches using artificial intelligence. Manufacturer information on IOL design and IOL power recorded as part of quality control could improve calculations, especially for higher IOL powers. With modern measurement data, there is further potential for improvement in the determination of the axial length to the retinal pigment epithelium and by adopting a sum-of-segment approach. With the available data, the cornea can be assumed to be a thick lens. The Kane formula, the EVO 2.0 formula, the Castrop formula, the PEARL-DGS, formula and the OKULIX calculation software provide consistently good results for artificial lens calculations. Excellent refractive results can be achieved using these tools, with approximately 80% having an absolute prediction error within 0.50 dpt, at least in highly selected study populations. The Barrett Universal II formula also produces excellent results in the normal and long axial length range. For eyes with short axial lengths, the use of Barrett Universal II should be reconsidered; in this case, one of the methods mentioned above is preferable. Second Eye Refinement can also be considered in this patient population, in conjunction with established classic third generation formulae.

The impact of compliance among patients with diabetic macular oedema treated with intravitreal aflibercept: a 48-month follow-up study.

PURPOSE: This study aimed to compare anatomical and functional outcomes between patients with non-proliferative diabetic retinopathy (NPDR) with diabetic macular oedema (DME) who adhered to intravitreal aflibercept therapy and patients lost to follow-up (LTFU). METHODS: We enrolled 200 patients and recorded the interval between each procedure and the subsequent follow-up visit. Moreover, visual acuity (VA) and anatomical outcomes were measured at each follow-up examination. RESULTS: Among the patients, 103 (51%) patients adhered to intravitreal aflibercept therapy and follow-up examination while 97 (49%) patients were LTFU. Forty-six (47%) patients LTFU who returned for further treatment showed a significant decrease in VA from 0.51 (±0.46) to 0.89 (±0.38) logarithm of the minimum angle of resolution (logMAR) after 48 months (p = 0.004). Compared with the adherent group, the return group showed a worse VA at 48 months (p = 0.036). Further, 1 (1%) patient in the adherent group and 8 (17%) patients in the return group developed a proliferative DR. Patients who were LTFU had a 13.0 times greater chance to develop a proliferative DR (p = 0.022). CONCLUSIONS: Patients who did not adhere to intravitreal aflibercept therapy for DME showed significantly worse visual outcomes compared to patients with good therapy adherence. Moreover, patients with LTFU had a 13 times higher risk of developing a proliferative DR. Considering the potential disease progress, better strategies should be applied to optimize the functional outcome of patients at risk of reduced adherence.

Effect of Timing on Visual Outcomes in Fovea-Involving Retinal Detachments Verified by SD-OCT.

PURPOSE: To investigate the impact of surgical delay after the objectivation of the foveal status by spectral-domain optical coherence tomography (SD-OCT) on visual outcomes in patients with rhegmatogenous retinal detachment (RRD) with foveal involvement. METHODS: A retrospective dataset analysis of 508 eyes of 504 consecutive patients with primary RRD was performed. The primary outcome measure was the best-corrected visual acuity as a function of time between the assessment of the foveal status with SD-OCT upon initial examination at the department and RRD repair. RESULTS: In total, 188 eyes (37.0%) had a complete foveal detachment and 31 (6.1%) eyes had a bisected fovea by the retinal detachment. A hundred eyes with total foveal detachment received surgery within 24 h and 65 eyes between 24 h and 72 h. Visual outcomes for eyes with detached fovea were significantly better when treated within 24 h (0.47 ± 0.39) compared with those treated between 24 h and 72 h (0.84 ± 0.66; p=0.01) after objectivation of the foveal status with SD-OCT. Pars plana vitrectomy was performed in 174 (92.6%) eyes and scleral buckling surgery in 14 (7.4%) eyes with complete foveal involvement of RRD. CONCLUSIONS: Our findings suggest improved visual outcomes for patients receiving surgery within 24 h after a definitive diagnosis of fovea-involving RRD compared to surgical interventions that were further delayed.

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Treatment compliance and adherence among patients with diabetic retinopathy and age-related macular degeneration treated by anti-vascular endothelial growth factor under universal health coverage.

PURPOSE: To analyze and compare loss to follow-up (LTFU) rates between patients with diabetic retinopathy (DR) and those with neovascular age-related macular degeneration (nAMD) in patients, receiving treatment with anti-vascular endothelial growth factor (VEGF), under universal health coverage. METHODS: We retrospectively analyzed the relevant data of 1264 patients receiving anti-VEGF therapy, in this cohort study. The observation period ranged from September 01, 2015 to December 31, 2018. Intervals between each procedure and the subsequent follow-up examination were measured. Demographic data, visual acuity (VA), the type of transport for treatment access, and distance between the residence and clinic were evaluated as risk factors for LTFU. RESULTS: We collected data for 841 patients with nAMD (age, 81.0 (± 8.1 years)) and 423 patients with DR (age, 67.7 (± 12.1 years)). The rate of LTFU, for at least 6 months, was 28.8% and 2.9% for patients with DR and nAMD, respectively (p < 0.001). In the DR group, 18.9% patients were lost to follow-up exceeding > 12 months. Multivariate regression analysis showed that advanced age, lack of mobility, and need for assisted transport, poor final VA despite treatment, and decrease in vision during the observational period were independent risk factors for LTFU exceeding 12 months (p < 0.05). CONCLUSIONS: We found a high long-term LTFU rate for patients with DR, despite treatment under universal health coverage. Considering the risk of disease progression, particularly in patients with chronic DR, strategies for better compliance and adherence to therapy should be considered for optimized patient care.

Laser-Synthesized SERS Substrates as Sensors toward Therapeutic Drug Monitoring.

The synthesis by pulsed laser ablation and the characterization of both the surface nanostructure and the optical properties of noble metal nanoparticle-based substrates used in Surface Enhanced Raman Spectroscopy are discussed with reference to application in the detection of anti-epileptic drugs. Results on two representative drugs, namely Carbamazepine and Perampanel, are critically addressed.

Transcutaneous vagal nerve stimulatio (t-VNS): An adjunctive treatment option for refractory epilepsy.

PURPOSE: The aim of this trial was to investigate the efficacy and safety of transcutaneous vagal nerve stimulation (t-VNS) in the palliative treatment of drug resistant epileptic patients ineligible for surgery. METHODS: Twenty adult patients received four hours of t-VNS per day for six months (T1), followed by a two-month washout period (T2). The frequency and type of seizures recorded at T1 and T2 were compared with those occurring in the three months preceding study entry (T0). Responders (>30% reduction in the total number of seizures) subsequently received two hours of t-VNS per day for further six months (T3). All patients underwent electroencephalography (EEG) and completed the Quality of Life in Epilepsy questionnaire at baseline and T1. RESULTS: At T1 six patients were considered responders. In these patients, at T3 the average reduction in seizure frequency was 60% compared to T0 (p = 0.043), and 51% compared to T2 (p = 0.043). Responders had more often seizures with falls (5 of 6; 83.3%) compared with non-responders (3 of 14; 21.4%) (p = 0,010) and t-VNS reduced their frequency by a percentage ranging from 47.5 to 100%. There was no change in responders' EEG findings after stimulation. At the end of the trial, three responders continued t-VNS, one implanted VNS. CONCLUSIONS: t-VNS had no or minimal side effects and significantly reduced seizures in about one third of the enrolled patients. Further studies should be planned to assess whether t-VNS is a suitable tool to predict the efficacy of implanted VNS.

Advanced morphological neuroimaging study in lateral temporal lobe epilepsy: A multicentric study.

Lateral temporal lobe epilepsy (lTLE) is a rare condition characterized by auditory auras or receptive aphasia, negative MRI, and relatively benign evolution. With the low number of cases in the world, our objective was to analyze a cohort of sporadic cases with lTLE (slTLE), in order to investigate possible cerebral morphological alterations. Forty patients with lTLE (34.93±12.08years of age) and 38 healthy controls (CTRL, 34.55±9.08years of age) were enrolled from four tertiary Italian epilepsy centers, which provided brain MRI T1-weighted images following a standard protocol for patients with epilepsy. We performed group comparison by following different approaches: voxel-based morphometry (VBM, SPM8), cortical thickness (CT), and local gyrification index (lGI) (FreeSurfer 5.3). At a more conservative threshold (p<0.05, FWE correction), no significant differences between groups survived, neither in VBM nor CT/lGI. Multicenter studies have more power than smaller studies in conducting sophisticated evaluations of rare diseases, and further investigations are required to develop a full picture of this rare phenotype.

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

PARADISE 24 instrument: An observational study on psychosocial difficulties, quality of life, and disability levels in patients with epilepsy.

AIM: The aim of this observational study was to test the effectiveness of the PARADISE 24 instrument in describing the psychosocial difficulties (PSDs) reported by people with epilepsy, their relation with disability, and quality-of-life (QoL) levels and, overall, to explore a horizontal epidemiology methodology applied to a sample of patients with epilepsy. METHODS: A convenience sample of 80 adult patients with epilepsy was included in this cross-sectional study. Patients were interviewed using a structured protocol composed of demographic, clinical, and patient-reported outcome measures to collect PSDs associated with epilepsy. RESULTS: There were 80 patients, 40 females; mean age was 41.2years; mean disease duration was 18.7years; and mean number of AED was 2.09. Moderate severity rating according to clinicians' rating scale, low impact of comorbidities (mean: 2.36, SD: 2.97), high levels of QoL (mean: 30.00, SD: 4.4), medium levels of resilience (mean: 13.56, SD: 2.66), high levels of perceived empathy (mean: 15.05, SD: 4.74), poor or moderate perceived social support, and low levels of disability (mean: 10.85, SD: 10.05) were observed. The most frequently reported PSDs were related to tiredness (80%), emotional problems (73.75%), anxiety (68.75%), depressive mood (66.25%), and driving problems (61.25%). The EUROHIS-QOL (p=.003) had a negative significant relationship with PARADISE 24 while WHODAS-12 (p=.000) and CRS (p=.027) had a positive significant relationship with PARADISE 24. CONCLUSIONS: The PARADISE 24 permits data comparison and the creation of a complete description of a person's functioning and of all of his/her PSDs and allows better and more tailored interventions.

Electroencephalographic (EEG) Photoparoxysmal Responses Under 5 Years of Age: Diagnostic Implications and Peculiarities.

Electroencephalographic (EEG) photoparoxysmal response has been little investigated in very young patients. We studied 5055 patients aged less than 5 years with no acquired brain damage, who underwent EEG recording. We determined the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz photic stimulation. Fifty-three showed photoparoxysmal response and were diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9), and static disorders with a known or suspected genetic origin (17). Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5% subjects. In most patients with epileptic encephalopathies, photoparoxysmal response was a transient finding: in 53.2%, it failed to be replicated in the recordings performed more than 6 months after initial evaluation. Photoparoxysmal response is rare in patients aged less than 5 years and has some peculiarities such as occurrence with low-frequency stimuli. Its distribution in specific conditions indicates that photoparoxysmal response may be useful in diagnostic workup.

Mild Lafora disease: clinical, neurophysiologic, and genetic findings.

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty-three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow-up duration was 13.2 ± 8.0 years. NHLRC1 mutations were detected in 18 patients; EPM2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as "mild" and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography (EEG) and giant somatosensory evoked potentials, as compared to patients with typical LD. However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD. The occurrence of specific NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.

Self-rated and assessed cognitive functions in epilepsy: impact on quality of life.

AIM OF THE STUDY: To compare the effects of perceived and assessed cognitive functions on quality of life (QoL) in patients with epilepsy (PWE). METHODS: The study analyzed the data from a series of PWE who compiled the Quality of Life in Epilepsy-89 Inventory (QOLIE-89) and the Multiple Ability Self-Report Questionnaire (MASQ) for QoL and perceived cognitive abilities, respectively. The State-Trait Anxiety and Beck Depression inventories were used to assess mood. Neuropsychological tests evaluated abstract reasoning, attention, conceptual-motor tracking, constructional praxis, language, verbal and non-verbal memory, abstraction, category shifting, verbal fluency, and visual-spatial abilities. RESULTS: The QOLIE-89 overall score was predicted by the Mood and Attention and Executive Functions factors and MASQ scores, explaining 38, 6, and 4% of its variance, while disease duration, seizure frequency, and schooling determined 16%. The QOLIE-89 Psychosocial, Cognitive, and Physical Performance sub-domains related to mood. The Cognitive and Physical Performance factors also related to the MASQ and Attention and Executive Functions factor scores, respectively. CONCLUSIONS: In PWE, self-rated and assessed cognitive deficits may influence QoL, explaining 10% of its variance irrespective from mood and clinical variables. Treating cognitive deficits and their perception may help improve QoL.

Hemispherotomy in Rasmussen encephalitis: long-term outcome in an Italian series of 16 patients.

Surgical disconnection of the affected hemisphere is considered the treatment of choice for Rasmussen encephalitis (RE), however few data on long-term outcomes after disconnective surgery are available. We report on long-term seizure, cognitive and motor outcomes after disconnective surgery in 16 (8 M, 8 F) RE patients. Pre- and post-operative evaluations included long-term video-EEG monitoring, MRI, assessment of motor function, and cognitive evaluation. Hemispherotomy, by various techniques was used to obtain functional disconnection of the affected hemisphere. The patients, of median current age 23.5 years, range 12-33, were operated on between 1993 and 2009. Median age at disease onset was 5.8 years (range 3-11.4). Median time from seizure onset to surgery was 3.8 years, range 8 months to 21 years. Post-surgical follow-up was a median of 9.5 years, range 3-20. At surgery all patients were receiving two or more antiepileptic drugs (AEDs). All but three patients were seizure-free at latest follow-up. AEDs had been stopped in ten patients; in the remaining six AEDs were markedly reduced. Postural control improved in all patients. Gain in cognitive functioning was significantly (p=0.002) related to disease duration. The long-term outcomes, in terms of seizure control, motor improvement, and cognitive improvement provide important support for disconnective surgery as first choice treatment for RE.

Vagus nerve stimulation for drug-resistant Epilepsia Partialis Continua: report of four cases.

BACKGROUND: Vagus nerve stimulation (VNS) represents an adjunctive surgical option for adult and pediatric patients with drug-resistant epilepsy, who are not eligible for surgical resection or disconnection. However, little is known on its efficacy in the treatment of Epilepsia Partialis Continua (EPC), a rare but serious form of motor status epilepticus associated either with progressive or with non-evolving neurological diseases. PURPOSE AND METHODS: To evaluate the effect of VNS in a series of four children affected by medically unresponsive EPC secondary to chronic inflammatory encephalopathy (two cases), Rasmussen encephalitis (one case) and poliodystrophy (one case). RESULTS: After VNS implantation, the stimulation amplitude was progressively increased and, after a mean interval of 47 days, a partial reduction of EPC and associated focal seizures was observed in all patients. After a mean follow-up of three years, one child stopped EPC, two presented short and rare episodes and in one patient 2-3 residual seizures per day was reported. In all cases, reduction of epileptic activity was associated with mild improvement of motor and cognitive abilities. No serious side effects were reported. CONCLUSION: VNS may be considered as an option for EPC when medical treatment fails and other more invasive neurosurgical options are not feasible.