Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia). Study design: Prospective, multi-centre, observational study. Materials and methods: pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness. Results: A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 µm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness. Conclusion: The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 µm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

Validation of Optical Coherence Tomography Retinal Segmentation in Neurodegenerative Disease.

PURPOSE: This study assessed agreement between an automated spectral-domain optical coherence tomography (SD-OCT) retinal segmentation software and manually corrected segmentation to validate its use in a prospective clinical study of neurodegenerative diseases (NDD). METHODS: The sample comprised 30 subjects with NDD, including vascular cognitive impairment, frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. Macular SD-OCT scans were acquired and segmented using Heidelberg Spectralis. For the central foveal B scan of each eye, eight segmentation lines were examined to determine the proportion of each line that the software erroneously delineated. Errors in four lines were manually corrected in all B scans spanning a 6-mm circle centered on the foveola. Mean volume and thickness measurements for four retinal layers (total retina, retinal nerve fiber layer [RNFL], inner retinal layers, and outer retinal layers) were obtained before and after correction. RESULTS: The outer plexiform layer line had one of the lowest mean error ratios (2%), while RNFL had the highest (23%). Agreement between automated software and trained observer was excellent (ICC > 0.98) for retinal thickness and volume of all layers. Mean volume differences between software and observers for the four layers ranged from -0.003 to 0.006 mm3. Mean thickness differences ranged from -1.855 to 1.859 µm. CONCLUSIONS: Despite occasional small errors in software-generated retinal sublayer segmentation, agreement was excellent between software-derived and observer-corrected mean volume and thickness sublayer measurements. TRANSLATIONAL RELEVANCE: Automated SD-OCT segmentation software generates valid measurements of retinal layer volume and thickness in NDD subjects, thereby avoiding the need to manually correct nonobvious delineation errors.

Evaluation of the SIPAT instrument to assess psychosocial risk in heart transplant candidates: A retrospective single center study.

OBJECTIVES: We evaluated the reliability of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in heart transplant (HT) recipients and explored its usefulness in predicting post-transplant outcomes. BACKGROUND: Pre-transplant psychosocial and behavioral risk is associated with post-transplant clinical outcomes. SIPAT is a risk assessment tool created for pre-transplant psychosocial evaluation. METHODS: Via retrospective chart review, three examiners applied the SIPAT to 51 adult HT recipients. Examiners blinded to SIPAT scores extracted data and interviewed clinicians for one-year post-transplant outcomes. Analysis included Intra-class correlation coefficient (ICC), Pearson's correlation coefficient and Chi-square. RESULTS: SIPAT demonstrated strong inter-rater reliability (ICC = 0.89, 95% CI = 0.76-0.96). Compared to those with SIPAT ratings of "Excellent/Good", the "Minimally Acceptable Candidate/High Risk" group was more likely to miss clinic visits (p = 0.004). CONCLUSIONS: The SIPAT tool had strong IRR. Less favorable SIPAT ratings were associated with nonadherence to clinic visits. Further study is warranted to determine association of SIPAT ratings to clinical outcomes.

Relationship between retinal blood flow and arterial oxygen.

KEY POINTS: Vascular reactivity, the response of the vessels to a vasoactive stimulus such as hypoxia and hyperoxia, can be used to assess the vascular range of adjustment in which the vessels are able to compensate for changes in PO2. Previous studies in the retina have not accurately quantified retinal vascular responses and precisely targeted multiple PaO2 stimuli at the same time as controlling the level of carbon dioxide, thus precluding them from modelling the relationship between retinal blood flow and oxygen. The present study modelled the relationship between retinal blood flow and PaO2, showing them to be a combined linear and hyperbolic function. This model demonstrates that the resting tonus of the vessels is at the mid-point and that they have great vascular range of adjustment, compensating for decreases in oxygen above a PETCO2 of 32-37 mmHg but being limited below this threshold. Retinal blood flow (RBF) increases in response to a reduction in oxygen (hypoxia) but decreases in response to increased oxygen (hyperoxia). However, the relationship between blood flow and the arterial partial pressure of oxygen has not been quantified and modelled in the retina, particularly in the vascular reserve and resting tonus of the vessels. The present study aimed to determine the limitations of the retinal vasculature by modelling the relationship between RBF and oxygen. Retinal vascular responses were measured in 13 subjects for eight different blood gas conditions, with the end-tidal partial pressure of oxygen (PETCO2) ranging from 40-500 mmHg. Retinal vascular response measurements were repeated twice; using the Canon laser blood flowmeter (Canon Inc., Tokyo, Japan) during the first visit and using Doppler spectral domain optical coherence tomography during the second visit. We determined that the relationship between RBF and PaO2 can be modelled as a combination of hyperbolic and linear functions. We concluded that RBF compensated for decreases in arterial oxygen content for all stages of hypoxia used in the present study but can no longer compensate below a PETCO2 of 32-37 mmHg. These vessels have a great vascular range of adjustment, increasing diameter (8.5% arteriolar and 21% total venous area) with hypoxia (40 mmHg P ETC O2; P < 0.001) and decreasing diameter (6.9% arteriolar and 23% total venous area) with hyperoxia (500 mmHg PETCO2; P < 0.001) to the same extent. This indicates that the resting tonus is near the mid-point of the adjustment ranges at resting PaO2 where sensitivity is maximum.

The impact of topical mydriatic ophthalmic solutions on retinal vascular reactivity and blood flow.

The impact of mydriatic agents on the standardized provocation of retinal vascular reactivity has not been systematically investigated. Our aim was to investigate the effect of commonly used mydriatic agents on the provoked vascular response of retinal arterioles. One eye was randomly selected for mydriasis from 10 healthy volunteers (age 23.3 ± 4.9 years). A single drop of: 1% tropicamide (T), or a combination of 0.8% tropicamide and 5% phenylephrine (TP), or 1% cyclopentolate (C) were instilled into the volunteers lower fornix at each of three visits. Volunteers underwent a standardized isocapnic hyperoxic provocation. Four retinal hemodynamic measurements were acquired with the Canon Laser Blood Flowmeter at equivalent positions on the superior temporal arteriole (STA) and inferior temporal arteriole (ITA) at baseline, during provocation and after recovery. Statistical analysis was performed using linear mixed-effect models. Pre- and post-dilation measurements indicated that pupil diameter increased with use of T, TP, C (all <0.001), while systolic blood pressure, diastolic blood pressure and intraocular pressure did not change significantly (all >0.05). In response to a standardized isocapnic hyperoxic challenge, blood vessel diameter, blood velocity and flow decreased in both the STA and ITA relative to baseline. Comparison between the change elicited by isocapnic hyperoxic gas stimuli with respect to blood vessel diameter, blood velocity, blood flow, were equivalent for each mydriatic agent in the STA (p = 0.66, p = 0.99, p = 0.99, respectively) and the ITA (p = 0.85, p = 0.80, p = 0.66, respectively). Furthermore, comparison between the change in the STA and ITA with respect to the above parameters showed equivalent responses in both vessels for each mydriatic agent: T (p = 0.92, p = 0.99, p = 0.35; respectively), TP (p = 0.89, p = 0.96, p = 0.62; respectively), and C (p = 0.87, p = 0.35, p = 0.56; respectively). The provoked retinal vascular reactivity response to standardized isocapnic hyperoxia was equivalent irrespective of the agent used to achieve mydriasis.

Human prefrontal cortical response to the meditative state: a spectroscopy study.

The effect of Qigong meditation on the hemodynamics of the prefrontal cortex was investigated by spectroscopy with a single-wavelength probe (650 nm) and confirmed by standard near-infrared spectroscopy with a dual-wavelength probe. Deoxyhemoglobin changes were recorded with the single-wavelength probe over the left prefrontal cortex during meditation by Qigong practitioners, and non-practitioners instructed in the technique. Practitioners showed a significant decrease in deoxyhemoglobin levels suggesting an increase in prefrontal activation during meditation. The results were confirmed in a second set of experiments with the standard dual-wavelength probe, in which significant differences in the decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations were observed in practitioners as compared with non-practitioners. The study thus provides evidence that Qigong meditation has a significant effect on prefrontal activation.