Retinal imaging with hand-held optical coherence tomography in older people with or without postoperative delirium after hip fracture surgery: A feasibility study.

INTRODUCTION: Postoperative delirium in older people may result from the interaction between intrinsic brain vulnerability (e.g. neurodegeneration) and precipitating factors (e.g. surgery induced cytokines). Intrinsic brain vulnerability may be overt (e.g. Alzheimer's disease) or preclinical. In cognitively intact older people presenting for surgery, identification of preclinical neurodegeneration using bedside tools could aid postoperative delirium risk stratification. Thinning of the circumpapillary retinal nerve fibre layer thickness is associated with neurodegenerative disorders e.g. Alzheimer's disease. We propose that thinning of the retinal nerve fibre layer may be present some older people with postoperative delirium due to preclinical neurodegeneration, albeit to a lesser extent than in overt dementia. OBJECTIVES: The primary objective: Feasibility of acquiring usable retinal images with the hand-held optical coherence device, at the bedside of older, hip fracture surgery patients. Secondary objective: Comparison of the circumpapillary retinal nerve fibre layer thickness between people who did/did not have postoperative delirium. Proportion of exclusions due to retinal pathology. METHOD: Feasibility study involving 30, cognitively intact, older people recovering from hip fracture surgery. Retinal images were obtained using the hand-held optical coherence tomography device at the participants' bedside. Imaging was deferred in participants who had postoperative delirium. RESULTS: Retinal images that could be assessed for circumpapillary retinal nerve fibre layer thickness were obtained in 26 participants (22 no postoperative delirium, 4 postoperative delirium). The mean circumpapillary retinal nerve fibre layer thickness was lower in the participants who had postoperative delirium compared to those who did not experience postoperative delirium (Mean (95% CI) of 76.50 (62.60-90.40) vs 89.19 (85.41-92.97) respectively). CONCLUSION: Retinal imaging at the patient's bedside, using hand-held OCT is feasible. Our data suggests that the circumpapillary retinal nerve fibre layer may be thinner in older people who experience postoperative delirium compared to those who do not. Further studies are required.

Preoperative inflammatory mediators and postoperative delirium: systematic review and meta-analysis.

BACKGROUND: Postoperative delirium has eluded attempts to define its complex aetiology and describe specific risk factors. The role of neuroinflammation as a risk factor, determined by measuring blood levels of preoperative 'innate' inflammatory mediator levels, has been investigated. However, results have been conflicting. We conducted a systematic review and meta-analysis of the evidence on associations between preoperative blood levels of inflammatory mediators and postoperative delirium in the older person. Influence of type of surgery was also assessed. METHODS: Original, low risk of bias studies, published in peer-reviewed journals, which fulfilled the eligibility criteria were included. Seventeen articles fulfilled study criteria. Data extraction, synthesis, and risk of bias analysis were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and quality in prognostic studies guidelines. Meta-analyses used a random-effects model. Inflammatory mediators included C-reactive protein, interleukin-6, -8, and -10, tumour necrosis factor-α, insulin-like growth factor-1, cortisol, and neopterin. Surgical groups were cardiac, noncardiac, and hip fracture. RESULTS: Higher preoperative interleukin-6 was associated with postoperative delirium with a standardised mean difference (95% confidence interval) of 0.33 (0.11-0.56) and P=0.003. Higher neopterin was also associated with postoperative delirium. CONCLUSIONS: The association of preoperative blood levels of inflammatory mediators with postoperative delirium may be influenced by the type of surgery and the specific mediator. The potential modulating effect of type of surgery, intrinsic brain vulnerability, and the complex interactions between inflammatory mediators and binding proteins will need to be considered in future studies. CLINICAL TRIAL REGISTRATION: CRD42019159471 (PROSPERO).

Optical coherence tomography in mild cognitive impairment - Systematic review and meta-analysis.

Thinning of retinal layers, measured using optical coherence tomography (OCT), is associated with some neurodegenerative disorders such as established Alzheimer's disease and multiple sclerosis. The evidence for retinal layer thinning in both mild cognitive impairment (MCI), a precursor of dementia, and delirium, a potential pre-clinical stage of neurodegenerative disorder, is unclear. We performed a systematic review of the associations, in older people, between retinal layer thickness changes (measured using OCT) and delirium or MCI compared to controls (Protocol registration ID (Prospero) CRD42019122165). We did not identify any relevant studies on delirium. This report is therefore a review of retinal nerve layer changes in mild cognitive impairment. Databases were searched using predetermined keywords such as mild cognitive impairment, retinal nerve fibre layer and delirium. Where there were sufficient data, meta-analyses were performed. Twenty-six relevant studies were identified on retinal layer thickness in people with MCI compared to controls. There was significant heterogeneity in the studies for all retinal layers investigated (retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIP), foveal thickness and macular volume). Analysis of 17 studies of mean RNFL thickness in MCI (n = 622) compared to controls (n = 1154), irrespective of the type of OCT device, demonstrated a significant thinning in MCI (SMD: - 0·42 and 95 % confidence interval: - 0·68 to - 0·16). This difference was non-significant when studies using only spectral-domain devices were analysed. Subgroup analysis of studies using spectral-domain devices in amnestic MCI diagnosed using comparable criteria, showed statistically significant thinning of RNFL in amnestic MCI (p = 0·02). Meta-analysis of foveal thickness did not show a significant difference between MCI and controls. In conclusion, there is some evidence of an association between retinal nerve fibre layer thinning and MCI. We found no data on the association between RNFL and delirium.