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Metabolic Brain Disease Oct 2022Recent advances in retinal imaging pathophysiology have shown a new function for biomarkers in Alzheimer's disease diagnosis and prognosis. The significant improvements... (Review)
Review
Recent advances in retinal imaging pathophysiology have shown a new function for biomarkers in Alzheimer's disease diagnosis and prognosis. The significant improvements in Optical coherence tomography (OCT) retinal imaging have led to significant clinical translation, particularly in Alzheimer's disease detection. This systematic review will provide a comprehensive overview of retinal imaging in clinical applications, with a special focus on biomarker analysis for use in Alzheimer's disease detection. Articles on OCT retinal imaging in Alzheimer's disease diagnosis were identified in PubMed, Google Scholar, IEEE Xplore, and Research Gate databases until March 2021. Those studies using simultaneous retinal imaging acquisition were chosen, while those using sequential techniques were rejected. "Alzheimer's disease" and "Dementia" were searched alone and in combination with "OCT" and "retinal imaging". Approximately 1000 publications were searched, and after deleting duplicate articles, 145 relevant studies focused on the diagnosis of Alzheimer's disease utilizing retinal imaging were chosen for study. OCT has recently been demonstrated to be a valuable technique in clinical practice as according to this survey, 57% of the researchers employed optical coherence tomography, 19% used ocular fundus imaging, 13% used scanning laser ophthalmoscopy, and 11% have used multimodal imaging to diagnose Alzheimer disease. Retinal imaging has become an important diagnostic technique for Alzheimer's disease. Given the scarcity of available literature, it is clear that future prospective trials involving larger and more homogeneous groups are necessary, and the work can be expanded by evaluating its significance utilizing a machine-learning platform rather than simply using statistical methodologies.
Topics: Humans; Alzheimer Disease; Retina; Tomography, Optical Coherence; Biomarkers
PubMed: 35290546
DOI: 10.1007/s11011-022-00927-4 -
JAMA Network Open Nov 2021The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations entailing a heavy clinical workload. Weight gain-based algorithms have the potential to minimize the need for binocular indirect ophthalmoscopy and have been evaluated in different setups with variable results to predict type 1 or severe ROP.
OBJECTIVE
To synthesize evidence regarding the ability of postnatal weight gain-based algorithms to predict type 1 or severe ROP.
DATA SOURCES
PubMed, MEDLINE, Embase, and the Cochrane Library databases were searched to identify studies published between January 2000 and August 2021.
STUDY SELECTION
Prospective and retrospective studies evaluating the ability of these algorithms to predict type 1 or severe ROP were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. This meta-analysis was performed according to the Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines.
MAIN OUTCOMES AND MEASURES
Ability of algorithms to predict type 1 or sever ROP was measured using statistical indices (pooled sensitivity, specificity, and summary area under the receiver operating characteristic curves, as well as pooled negative likelihood ratios and positive likelihood ratios and diagnostic odds ratios).
RESULTS
A total of 61 studies (>37 000 infants) were included in the meta-analysis. The pooled estimates for sensitivity and specificity, respectively, were 0.89 (95% CI, 0.85-0.92) and 0.57 (95% CI, 0.51-0.63) for WINROP (Weight, IGF-1 [insulinlike growth factor 1], Neonatal, ROP), 1.00 (95% CI, 0.88-1.00) and 0.60 (95% CI, 0.15-0.93) for G-ROP (Postnatal Growth and ROP), 0.95 (95% CI, 0.71-0.99) and 0.52 (95% CI, 0.36-0.68) for CHOP ROP (Children's Hospital of Philadelphia ROP), 0.99 (95% CI, 0.73-1.00) and 0.49 (95% CI, 0.03-0.74) for ROPScore, 0.98 (95% CI, 0.94-0.99) and 0.35 (95% CI, 0.22-0.51) for CO-ROP (Colorado ROP). The original PINT (Premature Infants in Need of Transfusion) ROP study reported a sensitivity of 0.98 (95% CI, 0.91-0.99) and a specificity of 0.36 (95% CI, 0.30-0.42). The pooled negative likelihood ratios were 0.19 (95% CI, 0.13-0.27) for WINROP, 0.0 (95% CI, 0.00-0.32) for G-ROP, 0.10 (95% CI, 0.02-0.53) for CHOP ROP, 0.03 (95% CI, 0.00-0.77) for ROPScore, and 0.07 (95% CI, 0.03-0.16) for CO-ROP. The pooled positive likelihood ratios were 2.1 (95% CI, 1.8-2.4) for WINROP, 2.5 (95% CI, 0.7-9.1) for G-ROP, 2.0 (95% CI, 1.5-2.6) for CHOP ROP, 1.9 (95% CI, 1.1-3.3) for ROPScore, and 1.5 (95% CI, 1.2-1.9) for CO-ROP.
CONCLUSIONS AND RELEVANCE
This study suggests that weight gain-based algorithms have adequate sensitivity and negative likelihood ratios to provide reasonable certainty in ruling out type 1 ROP or severe ROP. Given the implications of missing even a single case of severe ROP, algorithms with very high sensitivity (close to 100%) and low negative likelihood ratios (close to zero) need to be chosen to safely reduce the number of unnecessary examinations in infants at lower risk of severe ROP.
Topics: Algorithms; Birth Weight; Early Diagnosis; Female; Forecasting; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Neonatal Screening; Philadelphia; Prognosis; Prospective Studies; Retinopathy of Prematurity; Retrospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Weight Gain
PubMed: 34812847
DOI: 10.1001/jamanetworkopen.2021.35879 -
Journal of Medical Internet Research Aug 2021Virtual reality, augmented reality, and mixed reality make use of a variety of different software and hardware, but they share three main characteristics: immersion,... (Review)
Review
BACKGROUND
Virtual reality, augmented reality, and mixed reality make use of a variety of different software and hardware, but they share three main characteristics: immersion, presence, and interaction. The umbrella term for technologies with these characteristics is extended reality. The ability of extended reality to create environments that are otherwise impossible in the real world has practical implications in the medical discipline. In ophthalmology, virtual reality simulators have become increasingly popular as tools for surgical education. Recent developments have also explored diagnostic and therapeutic uses in ophthalmology.
OBJECTIVE
This systematic review aims to identify and investigate the utility of extended reality in ophthalmic education, diagnostics, and therapeutics.
METHODS
A literature search was conducted using PubMed, Embase, and Cochrane Register of Controlled Trials. Publications from January 1, 1956 to April 15, 2020 were included. Inclusion criteria were studies evaluating the use of extended reality in ophthalmic education, diagnostics, and therapeutics. Eligible studies were evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Relevant studies were also evaluated using a validity framework. Findings and relevant data from the studies were extracted, evaluated, and compared to determine the utility of extended reality in ophthalmology.
RESULTS
We identified 12,490 unique records in our literature search; 87 met final eligibility criteria, comprising studies that evaluated the use of extended reality in education (n=54), diagnostics (n=5), and therapeutics (n=28). Of these, 79 studies (91%) achieved evidence levels in the range 2b to 4, indicating poor quality. Only 2 (9%) out of 22 relevant studies addressed all 5 sources of validity evidence. In education, we found that ophthalmic surgical simulators demonstrated efficacy and validity in improving surgical performance and reducing complication rates. Ophthalmoscopy simulators demonstrated efficacy and validity evidence in improving ophthalmoscopy skills in the clinical setting. In diagnostics, studies demonstrated proof-of-concept in presenting ocular imaging data on extended reality platforms and validity in assessing the function of patients with ophthalmic diseases. In therapeutics, heads-up surgical systems had similar complication rates, procedural success rates, and outcomes in comparison with conventional ophthalmic surgery.
CONCLUSIONS
Extended reality has promising areas of application in ophthalmology, but additional high-quality comparative studies are needed to assess their roles among incumbent methods of ophthalmic education, diagnostics, and therapeutics.
Topics: Augmented Reality; Humans; Ophthalmology; Virtual Reality
PubMed: 34420929
DOI: 10.2196/24152 -
Survey of Ophthalmology 2022Retinal vascular diseases are a leading cause for blindness and partial sight certifications. By applying adaptive optics (AO) to conventional imaging modalities, the... (Meta-Analysis)
Meta-Analysis Review
Retinal vascular diseases are a leading cause for blindness and partial sight certifications. By applying adaptive optics (AO) to conventional imaging modalities, the microstructures of the retinal vasculature can be observed with high spatial resolution, hence offering a unique opportunity for the exploration of the human microcirculation. The objective of this systematic review is to describe the current state of retinal vascular biomarkers imaged by AO flood illumination ophthalmoscopy (FIO) and AO scanning laser ophthalmoscopy (SLO). A literature research was conducted in the PubMed and Scopus databases on July 9, 2020. From 217 screened studies, 42 were eligible for this review. All studies underwent a quality check regarding their content. A meta-analysis was performed for the biomarkers reported for the same pathology in at least three studies using the same modality. The most frequently studied vascular biomarkers were the inner diameter (ID), outer diameter (OD), parietal thickness (PT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR). The applicability of AO vascular biomarkers has been mostly explored in systemic hypertension using AO FIO and in diabetes using AO SLO. The result of the meta-analysis for hypertensive patients showed that WLR, PT, and ID were significantly different when compared to healthy controls, while WCSA was not (P < 0.001, P = 0.002, P < 0.001, and P = 0.070, respectively). The presented review shows that, although a substantial number of retinal vascular biomarkers have been explored in AO en face imaging, further clinical research and standardization of procedures is needed to validate such biomarkers for the longitudinal monitoring of arterial hypertension and other diseases.
Topics: Biomarkers; Humans; Ophthalmoscopy; Optics and Photonics; Retinal Diseases; Retinal Vessels
PubMed: 34090882
DOI: 10.1016/j.survophthal.2021.05.012 -
JAMA Ophthalmology Jan 2021Red reflex testing is a simple and inexpensive method implemented in many countries as an important part of infant screening for ocular pathologies. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Red reflex testing is a simple and inexpensive method implemented in many countries as an important part of infant screening for ocular pathologies.
OBJECTIVES
To review the literature on the diagnostic accuracy of the red reflex test in infant screening for ocular pathologies and to perform meta-analyses to provide summary estimates.
DATA SOURCES
The following literature databases were searched for English-language, peer-reviewed literature, published until April 19, 2020: Cochrane Central, PubMed/MEDLINE, Embase, Web of Science Core Collection, BIOSIS Previews, Current Contents Connect, Data Citation Index, Derwent Innovations Index, KCI-Korean Journal Database, Russian Science Citation Index, SciELO Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov.
STUDY SELECTION
Eligibility criteria were defined according to population (studies of consecutively screened infants), exposure (red reflex or Brückner test as the index test), comparator (any ophthalmological examination), and study type (any study with diagnostic test accuracy data).
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Data were extracted independently by 2 authors. For summary estimates of diagnostic test accuracy, the hierarchical summary receiver operating characteristics curve was used. Prevalence of ocular pathologies was introduced for a prevalence meta-analysis, which was then used in calculations of diagnostic accuracy of the red reflex test when applied in infant screening.
MAIN OUTCOMES AND MEASURES
True-positive, false-positive, true-negative, and false-negative findings; sensitivity; specificity; and positive and negative predictive values.
RESULTS
In this meta-analysis, 8713 unique infants from 5 unique studies were eligible for qualitative and quantitative review. All studies used the red reflex test without pupillary dilation and were compared with a reference test performed with pupillary dilation. For any ocular pathology, an estimated sensitivity of 7.5% (95% CI, 7.4%-7.5%) and specificity of 97.5% (95% CI, 97.5%-97.5%) was found. Focusing on ocular pathologies that required a medical or surgical intervention, sensitivity improved to 17.5% (95% CI, 0.8%-84.8%) and specificity remained high at 97.6% (95% CI, 87.7%-99.6%).
CONCLUSIONS AND RELEVANCE
These findings suggest that an abnormal red reflex finding most likely reflects an underlying ocular pathology. However, a normal red reflex finding during screening does not exclude ocular disease.
Topics: Humans; Infant; Infant, Newborn; Neonatal Screening; Ophthalmoscopes; Ophthalmoscopy; Predictive Value of Tests; Refraction, Ocular; Refractive Errors; Reproducibility of Results; Vision Screening; Vision, Ocular
PubMed: 33180103
DOI: 10.1001/jamaophthalmol.2020.4854 -
Acta Ophthalmologica May 2021To review studies focusing on cilioretinal arteries (CLRA) in order to assess the overall prevalence and establish the prevalence of CLRA in a Hungarian Caucasian...
PURPOSE
To review studies focusing on cilioretinal arteries (CLRA) in order to assess the overall prevalence and establish the prevalence of CLRA in a Hungarian Caucasian population. METHODS #1: Systematic literature review of published studies with at least 100 participants. METHODS #2: Non-mydriatic digital colour photographs were taken of 1000 consecutively enrolled healthy Caucasian young adult volunteers. Images were graded by two trained independent observers. Number and location of identified cilioretinal arteries were recorded and statistically analysed. RESULTS #1: Prevalence of CLRA ranges from 6.9% to 49.5%. Detection with fluorescein angiography yields the highest values followed by fundus photography and ophthalmoscopy. Unilateral presence of CLRA is between 70.30% and 93.65%, and temporal location is between 80.77% and 100%. RESULTS #2: We found at least one CLRA in 36.5% of the participants and in 22.75% of all the examined eyes. Cilioretinal arteries (CLRA) were unilateral in 75.34% and bilateral in 24.66%. Of all the identified CLRA, 96.16% were originating from the temporal rim of the optic disc. We identified at least one temporal CLRA supplying the macula in 28% of the participants and 16.95% of the examined eyes.
CONCLUSION
Prevalence of CLRA varies depending on identification method. Unilateral presence is unequivocally more frequent similarly to temporal location. From a risk of bias standpoint, high-quality studies are rare. Our data on the distribution pattern of CLRA are similar to that in the international literature. Based on our findings, we assume that slightly more than one-third of the Hungarian Caucasian population has a CLRA.
Topics: Ciliary Arteries; Cross-Sectional Studies; Female; Humans; Male; Prevalence; Prospective Studies; Retinal Artery; Retinal Diseases
PubMed: 32833328
DOI: 10.1111/aos.14592 -
International Journal of Ophthalmology 2020Non-simulator-based examination methods of the fundal examination have shown to be cost-effective. We reviewed different non-simulator-based direct fundoscopy... (Review)
Review
Non-simulator-based examination methods of the fundal examination have shown to be cost-effective. We reviewed different non-simulator-based direct fundoscopy examination methods used in undergraduate curricula and their outcomes. PubMed (MEDLINE) and Cochrane Database of Systematic Reviews were searched using standard Medical Subject Heading (MeSH) terms ophthalmoscopy, medical education, undergraduate medical education, medical student, educational assessment and learning. The search included publications until 28 February 2019. We obtained 34 articles after screening abstracts; of them, 12 articles were included in the qualitative synthesis. The studies were comprised of diverse teaching methods which included fundal photograph matching with corresponding eye, continuous education using community-based eye clinics, formal instructions and demonstrations prior to skills training, ophthalmoscopy skills practice using eye pathologies, teaching versus conventional ophthalmoscopy and group-based teaching. We concluded that non-simulator-based techniques such as use of fundal photograph matching of an eye of a volunteer, introduction to eye pathologies, smaller student groups and formal instructions with video demonstrations prior to skills training were highly effective in teaching direct ophthalmoscopy for undergraduate medical students.
PubMed: 32399420
DOI: 10.18240/ijo.2020.04.20 -
International Journal of Molecular... Apr 2020The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used.
METHODS
In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a- and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays.
RESULTS
original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave (Hedges' g 1.181 (0.471-1.892), = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 versus in the range of 10) resulted in a significantly increased effect on vision-based behavior as well. The origin of cells mattered as well. A significantly increased effect was found on vision-based behavior when using ARPE-19 and OpRegen RPE.
CONCLUSIONS
This systematic review shows that RPE transplantation in animal models for retinal degeneration significantly increases a- and b- wave amplitudes and improves vision-related behavior. These effects appear to be more pronounced in young animals, when the number of transplanted cells is larger and when ARPE-19 and OpRegen RPE cells are used. We further emphasize that there is an urgent need for improving the reporting and methodological quality of animal experiments, to make such studies more comparable.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Models, Animal; Publication Bias; Retinal Degeneration; Retinal Pigment Epithelium; Treatment Outcome
PubMed: 32295315
DOI: 10.3390/ijms21082719 -
The Journal of Antimicrobial... Mar 2020Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality.
BACKGROUND
Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality.
OBJECTIVES
To assess the impact of implementing an evidence-based package of measures (bundle) on the quality of care and outcomes of candidaemia.
METHODS
A systematic review of the literature was performed to identify measures related to better outcomes in candidaemia. Eight quality-of-care indicators (QCIs) were identified and a set of written recommendations (early treatment, echinocandins in septic shock, source control, follow-up blood culture, ophthalmoscopy, echocardiography, de-escalation, length of treatment) was prospectively implemented. The study was performed in 11 tertiary hospitals in Spain. A quasi-experimental design before and during bundle implementation (September 2016 to February 2018) was used. For the pre-intervention period, data from the prospective national surveillance were used (May 2010 to April 2011).
RESULTS
A total of 385 and 263 episodes were included in the pre-intervention and intervention groups, respectively. Adherence to all QCIs improved in the intervention group. The intervention group had a decrease in early (OR 0.46; 95% CI 0.23-0.89; P = 0.022) and overall (OR 0.61; 95% CI 0.4-0.94; P = 0.023) mortality after controlling for potential confounders.
CONCLUSIONS
Implementing a structured, evidence-based intervention bundle significantly improved patient care and early and overall mortality in patients with candidaemia. Institutions should embrace this objective strategy and use the bundle as a means to measure high-quality medical care of patients.
Topics: Candidemia; Humans; Prospective Studies; Quality of Health Care; Shock, Septic; Spain
PubMed: 31819991
DOI: 10.1093/jac/dkz491 -
Retina (Philadelphia, Pa.) Oct 2019To reclassify fundus autofluorescence (FAF) patterns around geographic atrophy (GA) based on GA progression rates. (Meta-Analysis)
Meta-Analysis
PURPOSE
To reclassify fundus autofluorescence (FAF) patterns around geographic atrophy (GA) based on GA progression rates.
METHODS
MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov, and PubMed were searched for studies reporting GA progression rates among different FAF patterns, such as "None," "Focal," "Banded," "Patchy," "Diffuse Nontrickling," and "Diffuse Trickling." The GA radius growth rate among different FAF patterns was compared, and a GA growth function for each group was derived. To account for the patients' different entry times, a horizontal translation factor was introduced to shift each data subset from "time after enrollment" to "duration of GA."
RESULTS
Seven studies with 496 eyes were included. Based on GA radius growth rates, the six FAF patterns were clustered into four groups with a high correlation coefficient within each group: Group 1, None, 0.061 mm/year (r = 0.996), Group 2, Focal, 0.105 mm/year (r = 0.987), Group 3, Banded, Patchy, and Diffuse Nontrickling, 0.149 mm/year (r = 0.993), and Group 4, "Diffuse Trickling, 0.245 mm/year (r = 0.997).
CONCLUSION
This meta-analysis suggested that the six FAF patterns can be coalesced into four groups based on lesion progression rates. Simplification of the reclassified FAF patterns may shed light on the GA natural history and assist in the design of clinical trials.
Topics: Disease Progression; Fluorescein Angiography; Fundus Oculi; Geographic Atrophy; Humans; Ophthalmoscopy; Retina
PubMed: 30829988
DOI: 10.1097/IAE.0000000000002480