Katie M. Hallahan

Bilateral subthalamic stimulation impairs cognitive ^motor performance in Parkinson's disease patients

Deep brain stimulation (DBS) is a surgical procedure that has been shown effective in improving the cardinal motor signs of advanced Parkinsons disease, however, declines in cognitive function have been associated with bilateral subthalamic nucleus (STN) DBS. Despite the fact that most activities of daily living clearly have motor and cognitive components performed simultaneously, postoperative assessments of cognitive and motor function occur, in general, in isolation of one another. The primary aim of this study was to determine the effects of unilateral and bilateral STN DBS on upper extremity motor function and cognitive performance under single- and dual-task conditions in advanced Parkinsons disease patients. Data were collected from eight advanced Parkinsons disease patients between the ages of 48 and 70 years (mean 56.5) who had bilaterally placed STN stimulators. Stimulation parameters for DBS devices were optimized clinically and were stable for at least 6 months prior to study participation. Data were collected while patients were Off anti-parkinsonian medications under three stimulation conditions: Off stimulation, unilateral DBS and bilateral DBS. In each stimulation condition patients performed a cognitive (n-back task) and motor (force tracking) task under single- and dual-task conditions. During dual-task conditions, patients performed the n-back and force-maintenance task simultaneously. Under relatively simple dual-task conditions there were no differences in cognitive or motor performance under unilateral and bilateral stimulation. As dual-task complexity increased, cognitive and motor performance was significantly worse with bilateral compared with unilateral stimulation. In the most complex dual-task condition (i.e. 2-back + force tracking), bilateral stimulation resulted in a level of motor performance that was similar to the Off stimulation condition. Significant declines in cognitive and motor function under modest dual-task conditions with bilateral but not with unilateral STN DBS suggest that unilateral procedures may be an alternative to bilateral DBS for some patients, in particular, those with asymmetric symptomology. From a clinical perspective, these results underscore the need to assess cognitive and motor function simultaneously during DBS programming as these conditions may better reflect the context in which daily activities are performed.

Discriminant Value of Custom Ocular Response Analyzer Waveform Derivatives in Keratoconus

PURPOSE To evaluate the performance of corneal hysteresis (CH), corneal resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA) variables in distinguishing keratoconus (KC) from the nondiseased state. DESIGN Retrospective case series. PARTICIPANTS Fifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil. METHODS Sixteen candidate variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior. Area under the receiver operating characteristic curve (AUC) and the Z statistic were used to compare diagnostic performance. MAIN OUTCOME MEASURES Discriminant value of standard and derived ORA variables as measured by AUC. RESULTS Fifteen of 16 candidate variables performed significantly better than chance (AUC, >0.5) at discriminating KC. Diagnostic performance was greatest for a custom variable related to the depth of deformation as defined by the minimum applanation signal intensity during corneal deformation (concavity(min); mean AUC ± standard error, 0.985 ± 0.002) and a new measure incorporating the pressure-deformation relationship of the entire response cycle (hysteresis loop area, 0.967 ± 0.002). Z statistics assessing the discriminative value of each of the top 5 variables demonstrated superiority to CH (AUC, 0.862 ± 0.002). Concavity(min) had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity, 91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated the most consistent relationships to KC severity. CONCLUSIONS Investigator-derived ORA variables related to the depth of deformation and the pressure-deformation relationship demonstrated very high test accuracy for detecting the presence of KC. Beyond their diagnostic value, the candidate variables described in this report provide mechanistic insight into the nature of the ORA signal and the characteristic changes in corneal dynamics associated with KC.

Changes in custom biomechanical variables after femtosecond laser in situ keratomileusis and photorefractive keratectomy for myopia

Purpose To analyze changes in new biomechanical descriptors with myopic femtosecond laser–assisted laser in situ keratomileusis (LASIK), compare them with the biomechanical response after photorefractive keratectomy (PRK) with similar levels of myopic ablation, and evaluate correlations between changes in custom variables and biomechanically relevant variables. Setting Cleveland Clinic, Cleveland, Ohio, USA. Design Cohort study. Methods Custom biomechanical variables from the Optical Response Analyzer were assessed preoperatively and 1 and 3 months postoperatively. Differences between preoperative values and postoperative values were determined. Intraindividual change (preoperative value minus postoperative value) was calculated and compared with changes after PRK. The correlation of the change in each custom biomechanical variable with the preoperative central corneal thickness, residual stromal bed tissue ablated, and percentage of tissue depth altered was also studied. Results The study enrolled 156 eyes of 156 consecutive patients. Fifteen variables changed significantly after femtosecond myopic LASIK and were stable postoperatively because no significant difference was shown between 1‐month values and 3‐month values. Comparison of the changes in biomechanical variables between LASIK and PRK eyes showed no significant differences. Surgical changes in several custom biomechanical variables correlated with the percentage of tissue depth altered. Conclusions The results provide the first reference values for a more comprehensive panel of indicators of the biomechanical response to myopic LASIK and PRK. Changes in custom variables reflected a consistent decrease in corneal biomechanical resistance to deformation after myopic femtosecond LASIK and PRK. For comparable attempted corrections, biomechanical changes were comparable between femtosecond laser–assisted LASIK and PRK. Financial Disclosure(s) Proprietary or commercial disclosures are listed after the references.

Effects of corneal cross-linking on ocular response analyzer waveform-derived variables in keratoconus and postrefractive surgery ectasia.

Purpose: To assess changes in Ocular Response Analyzer (ORA) waveforms after UVA/riboflavin corneal collagen cross-linking (CXL) using investigator-derived and manufacturer-supplied morphometric variables in patients with keratoconus (KC) and postrefractive surgery ectasia. Design: Prospective randomized trial of a standard epithelium-off CXL protocol. Participants: Patients with progressive KC (24 eyes of 21 patients) or postrefractive surgery ectasia (27 eyes of 23 patients) were enrolled. Methods: Replicate ORA measurements were obtained before and 3 months after CXL. Pretreatment and posttreatment waveform variables were analyzed for differences by paired Student t tests using measurements with the highest waveform scores. Main Outcome Measures: Corneal hysteresis, corneal resistance factor, 37-s generation manufacturer-supplied ORA variables, and 15 investigator-derived ORA variables. Results: No variables were significantly different 3 months after CXL in the KC group, and no manufacturer-supplied variables changed significantly in the postrefractive surgery ectasia group. Four custom variables (ApplanationOnsetTime, P1P2avg, Impulse, and Pmax) increased by small but statistically significant margins after CXL in the postrefractive surgery ectasia group. Conclusions: Changes in a small subset of investigator-derived variables suggested an increase in corneal bending resistance after CXL. However, the magnitudes of these changes were low and not commensurate with the degree of clinical improvement or prior computational estimates of corneal stiffening in the same cohort over the same period. Available air-puff–derived measures of the corneal deformation response underestimate the biomechanical changes produced by CXL.

Enhanced combined tomography and biomechanics data for distinguishing forme fruste keratoconus

PURPOSE To evaluate the performance of the Ocular Response Analyzer (ORA) (Reichert Ophthalmic Instruments, Depew, NY) variables and Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany) tomographic parameters in differentiating forme fruste keratoconus (FFKC) from normal corneas, and to assess a combined biomechanical and tomographic parameter to improve outcomes. METHODS Seventy-six eyes of 76 normal patients and 21 eyes of 21 patients with FFKC were included in the study. Fifteen variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior and 37 ORA waveform parameters were tested. Sixteen tomographic parameters from Pentacam HR were tested. Logistic regression was used to produce a combined biomechanical and tomography linear model. Differences between groups were assessed by the Mann-Whitney U test. The area under the receiver operating characteristics curve (AUROC) was used to compare diagnostic performance. RESULTS No statistically significant differences were found in age, thinnest point, central corneal thickness, and maximum keratometry between groups. Twenty-one parameters showed significant differences between the FFKC and control groups. Among the ORA waveform measurements, the best parameters were those related to the area under the first peak, p1area1 (AUROC, 0.717 ± 0.065). Among the investigator ORA variables, a measure incorporating the pressure-deformation relationship of the entire response cycle was the best predictor (hysteresis loop area, AUROC, 0.688 ± 0.068). Among tomographic parameters, Belin/Ambrósio display showed the highest predictive value (AUROC, 0.91 ± 0.057). A combination of parameters showed the best result (AUROC, 0.953 ± 0.024) outperforming individual parameters. CONCLUSIONS Tomographic and biomechanical parameters demonstrated the ability to differentiate FFKC from normal eyes. A combination of both types of information further improved predictive value. [J Refract Surg. 2016;32(7):479-485.].

Reducing cognitive–motor declines associated with bilateral subthalamic deep brain stimulation through computational modelling in a parkinson's disease patient

Bilateral subthalamic (STN) deep brain stimulation (DBS) provides symptom relief for the majority of well-screened advanced Parkinsons disease (PD) patients.1 However, we have recently shown that bilateral STN DBS may result in significant declines in cognitive–motor performance of PD patients.2 The spread of current to non-motor areas of the STN may be responsible for cognitive and cognitive–motor declines. While guidelines exist on stimulation parameter settings that are typically effective, it is not practical to evaluate each of the thousands of stimulation parameter combinations possible. Therefore, the therapeutic benefit achieved with DBS is dependent on the intuitive skill and experience of the programming clinician. To assist the programming process, we developed Windows-based software tools that enable 3D visualisation of the volume of tissue activated (VTA) by DBS.3 The goal of this study was to compare two methods of DBS programming, the typical clinical method and our computational approach, on cognitive–motor performance in an advanced PD patient. A 58-year-old right-handed male with an 8-year history of PD underwent simultaneous bilateral STN-DBS 14 months prior to study participation. His stimulation parameters were optimised by traditional clinical methods and were stable for the 6 months prior to study participation. This patient did not have any history of cognitive deficits or postoperative changes in cognitive function based on neuropsychological testing. Blinded UPDRS-III evaluations were performed Off DBS and On DBS using previously determined clinical DBS parameters while the patient was off antiparkinsonian medication for 12 h. Under these conditions, the patient demonstrated a 45% reduction (improvement) in the UPDRS III with DBS on when compared with off. Cognitive–motor performance was quantified using a dual-task paradigm.2 …