Optimizing Stimulation and Analysis Protocols for Neonatal fMRI

The development of brain function in young infants is poorly understood. The core challenge is that infants have a limited behavioral repertoire through which brain function can be expressed. Neuroimaging with fMRI has great potential as a way of characterizing typical development, and detecting abnormal development early. But, a number of methodological challenges must first be tackled to improve the robustness and sensitivity of neonatal fMRI. A critical one of these, addressed here, is that the hemodynamic response function (HRF) in pre-term and term neonates differs from that in adults, which has a number of implications for fMRI. We created a realistic model of noise in fMRI data, using resting-state fMRI data from infants and adults, and then conducted simulations to assess the effect of HRF of the power of different stimulation protocols and analysis assumptions (HRF modeling). We found that neonatal fMRI is most powerful if block-durations are kept at the lower range of those typically used in adults (full on/off cycle duration 25-30s). Furthermore, we show that it is important to use the age-appropriate HRF during analysis, as mismatches can lead to reduced power or even inverted signal. Where the appropriate HRF is not known (for example due to potential developmental delay), a flexible basis set performs well, and allows accurate post-hoc estimation of the HRF

Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies

Acceptance and Perception of Artificial Intelligence Usability in Eye Care (APPRAISE) for Ophthalmologists: A Multinational Perspective

Background: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract. Methods: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning. Results: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83. Conclusion: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology

COVID-19 : special precautions in ophthalmic practice and FAQs on personal protection and mask selection

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Factors associated with variability in response of diabetic macular oedema after intravitreal triamcinolone

Purpose: To identify factors associated with variability in anatomical and functional response of diabetic macular oedema (DMO) after 4 mg of intravitreal triamcinolone acetonide (ivTA), and for recurrence of macular oedema. Design: Pooled analysis of individual data from two randomized controlled trials. Methods: This was a multicentre study involving 107 eyes with DMO administered 4 mg ivTA. Predictive factors for response to treatment were evaluated with linear regression analysis. Factors associated with time to recurrence of oedema were studied with Cox proportional hazards modelling. Main outcome measures were maximum improvement in optical coherence tomography (OCT)-measured central foveal thickness (CFT) and best-corrected visual acuity (BCVA), final CFT and BCVA at 12 months and time to oedema recurrence. Results: Greater reduction of retinal thickening occurred in eyes with worse baseline thickening (P < 0.001). There was also greater improvement of visual acuity in eyes with poorer preoperative BCVA levels (P < 0.001). Age, duration of oedema and previous macular laser treatment had no significant effect on maximal BCVA or CFT improvement. Eyes given 4 mg triamcinolone alone were more likely to develop recurrence of oedema at 12 months than those given a combination of 4mg triamcinolone plus sequential laser (hazard ratio 2.60 [95% confidence interval: 1.45-4.67]). Conclusion: Baseline OCT-measured retinal thickening and BCVA are important predictors of maximal anatomical and functional response of DMO to ivTA, respectively. Combination treatment strategy using sequential laser therapy may have a role in delaying recurrence of oedema after triamcinolone. © 2009 The Authors Journal compilation © 2009 Royal Australian and New Zealand College of Ophthalmologists.link_to_subscribed_fulltex

Different optineurin mutation pattern in primary open-angle glaucoma

PURPOSE. The optineurin gene (OPTN) is the second gene besides MYOC in which mutations have been identified to be associated with primary open-angle glaucoma (POAG). In this study, sequence alterations in the OPTN gene associated with POAG in Chinese subjects were investigated. METHODS. All the coding exons of OPTN were screened, including the intron-exon boundaries, for sequence alterations in a Chinese sample of 119 sporadic patients with POAG and 126 unrelated control subjects by polymerase chain reaction-conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS. Sixteen sequence changes were identified: 3 had been reported (T34T, M98K, and R545Q) and 13 were novel (T49T, E103D, V148V, P199P, T202T, H486R, IVS6-5T→C, IVS6-10G→A, IVS7+24G→A, IVS8+20G→A, IVS13+21C→G, IVS15+10G→, and IVS15-48C→A). Among them, only E103D, H486R, V148V, and IVS13+21C→G were found exclusively in patients with POAG, whereas P199P, T202T, and IVS8+20G→A were present only in control subjects. The genotype of IVS7+24G→A showed a significant association with POAG (P = 0.02, Fisher two-tailed exact test) and with and increased cup-to-disc ratio in these patients (P = 0.005, Mann-Whitney test). CONCLUSIONS. The findings in the current study enrich the evidence on the OPTN gene as a causative gene for POAG and suggest a different mutation pattern of OPTN in Chinese than in whites. The wide spectrum of putative mutations detected in this study suggests that both structural and functional disruptions in OPTN may contribute to the pathogenesis of glaucoma.link_to_subscribed_fulltex