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Eye (London, England) May 2021To comprehensively assess diabetic retinopathy neurodegeneration (DRN) as quantified by retinal neuronal and axonal layers measured with spectral-domain optical... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To comprehensively assess diabetic retinopathy neurodegeneration (DRN) as quantified by retinal neuronal and axonal layers measured with spectral-domain optical coherence tomography (SD-OCT) in subjects with diabetes mellitus (DM).
METHODS
Articles on the topic of examining macular ganglion cell-inner plexiform layer (m-GCIPL), macular retinal nerve fibre layer (m-RNFL), macular ganglion cell complex (m-GCC), and peripapillary RNFL (p-RNFL) measured with SD-OCT in DM subjects without DR (NDR) or with non-proliferative DR (NPDR) were searched in PubMed and Embase up to November 31, 2019. Standardized mean difference (SMD) as effect size were pooled using random-effects model.
RESULTS
Thirty-six studies searched from online databases and the CUHK DM cohort were included in the meta-analysis. In the comparison between NDR and control, macular measures including mean m-GCIPL (SMD = -0.26, p = 0.003), m-RNFL (SMD = -0.26, p = 0.046), and m-GCC (SMD = -0.28; p = 0.009) were significantly thinner in the NDR group. In the comparison between NPDR and NDR, only mean p-RNFL was significantly thinner in the NPDR group (SMD = -0.27; p = 0.03), but not other macular measures.
CONCLUSIONS
Thinning of retinal neuronal and axonal layers at macula as measured by SD-OCT are presented in eyes with NDR, supporting DRN may be the early pathogenesis in the DM patients without the presence of clinical signs of DR. In the future, these SD-OCT measures may be used as surrogates of DRN to stratify DM patients with a high risk of DR, and may be used as a therapeutic target if neuroprotection treatment for DR is available.
Topics: Humans; Macula Lutea; Nerve Fibers; Retina; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 32581390
DOI: 10.1038/s41433-020-1020-z -
Ophthalmology May 2020To summarize the rates of atrophy, risk factors, and atrophy-associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received...
TOPIC
To summarize the rates of atrophy, risk factors, and atrophy-associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (VEGF) treatment for macular neovascularization (MNV).
CLINICAL RELEVANCE
Age-related macular degeneration is a leading cause of vision loss worldwide, and VEGF inhibitors are the primary treatment for nAMD. However, atrophy is observed frequently in eyes treated with anti-VEGF therapy, prompting questions regarding a causative role for these therapies in atrophy development.
METHODS
PubMed was searched for articles published in the past 5 years (January 1, 2014, through January 10, 2019). Studies including atrophy outcome(s) in patients with age-related macular degeneration who received anti-VEGF treatment were included. Review articles, retrospective studies, case reports or studies, preclinical studies, prevalence data reports, and non-English studies were excluded. Randomization was not required.
RESULTS
Overall, 145 studies were identified; 29 publications were included, with cohorts ranging from 8 to 1185 eyes. Imaging methods used to assess atrophy varied across studies. All studies confirmed the occurrence of atrophy, and when available, longitudinal data from the included studies demonstrated an increase in atrophy incidence over time. Key risk factors or phenotypes associated with atrophy were fellow eye atrophy, reticular pseudodrusen, increased injections, and type 3 lesion. In addition, visual acuity loss was noted with foveal atrophy.
DISCUSSION
All studies demonstrated that atrophy occurs in the context of MNV treated with anti-VEGF therapy; however, it is not clear whether anti-VEGF treatment is causative of atrophy versus being associated with atrophy development. The included studies were not designed or powered to assess atrophy as a primary outcome. In addition, it is difficult to determine whether prognostic factors directly affect atrophy. Furthermore, patient populations in clinical trials do not necessarily represent real-world patients. Although phenotypes and risk factors may help to identify those at greater risk of atrophy developing, it is important to recognize that adequately treating exudative MNV remains the best option to optimize vision outcomes in patients with nAMD, particularly given the risk of vision loss with undertreatment observed in the real world.
Topics: Angiogenesis Inhibitors; Atrophy; Choroidal Neovascularization; Humans; Intravitreal Injections; Photoreceptor Cells, Vertebrate; Randomized Controlled Trials as Topic; Retinal Pigment Epithelium; Retrospective Studies; Risk Factors; Vascular Endothelial Growth Factor A; Wet Macular Degeneration
PubMed: 32081493
DOI: 10.1016/j.ophtha.2019.11.010 -
European Journal of Neurology Mar 2021Retinal pathological changes may precede or accompany the deterioration of brain tissue in Parkinson's disease (PD). The purpose of this meta-analysis was to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Retinal pathological changes may precede or accompany the deterioration of brain tissue in Parkinson's disease (PD). The purpose of this meta-analysis was to assess the usefulness of optical coherence tomography (OCT) measurements as potential imaging biomarkers for PD.
METHODS
PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched for observational studies (published prior to 30 May 2020) comparing the OCT measurements between PD patients and healthy controls (HCs). Our main end-points were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex thickness, macular thickness and macular volume. Pooled data were assessed by use of a random-effects model.
RESULTS
A total of 36 observational studies were identified that included 1712 patients with PD (2548 eyes) and 1778 HCs (2646 eyes). Compared with the HC group, the PD group showed a significant reduction in mean pRNFL thickness (weighted mean difference [WMD] -3.51 μm, 95% confidence interval [CI] -4.84, -2.18; p = 0.000), all quadrants at the pRNFL (WMD range -7.65 to -2.44 μm, all p < 0.05), macular fovea thickness (WMD -5.62 μm, 95% CI -7.37, -3.87; p = 0.000), all outer sector thicknesses at the macula (WMD range -4.68 to -4.10 μm, all p < 0.05), macular volume (WMD -0.21 mm , 95% CI -0.36, -0.06; p < 0.05) and macular ganglion cell complex thickness (WMD -4.18 μm, 95% CI -6.07, -2.29; p < 0.05).
CONCLUSIONS
Our pooled data confirmed robust associations between retinal OCT measurements and PD, highlighting the usefulness of OCT measurements as potential imaging biomarkers for PD.
Topics: Biomarkers; Cross-Sectional Studies; Humans; Nerve Fibers; Parkinson Disease; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 33107159
DOI: 10.1111/ene.14613 -
Pain Oct 2019Wide dynamic range (WDR) neurons of the spinal dorsal horn respond to a wide range of innocuous and noxious mechanical stimulation and encode the intensity of mechanical...
Wide dynamic range (WDR) neurons of the spinal dorsal horn respond to a wide range of innocuous and noxious mechanical stimulation and encode the intensity of mechanical stimuli as changes in firing rate. However, there are inconsistent findings regarding whether WDR neuron stimulus encoding activity is altered in pathological pain states. This inconsistency may arise from differences in the pain models used or in the experimental conditions themselves. In this study, we use a meta-regression approach to examine which variables modulate and determine WDR activity. We pooled data from in vivo electrophysiological studies of WDR activity evoked by von Frey filament stimulation of the hind paw in rats across a number of pathological pain models. We observed that WDR firing rate was better predicted by the calculated pressure of von Frey stimulation rather than applied filament force, as reported in all studies. The pressure-evoked firing rate of WDR neurons was not altered by any experimental pain model except for arthritis and inflammation models, where mechanical stimuli evoked a higher firing rate than controls. Conversely, there was a consistent increase in the spontaneous firing rate of WDR neurons in neuropathic pain, arthritis and inflammation, and chemoneuropathy pain models. Overall, these data indicate that changes in WDR encoding of applied pressure are unlikely to significantly contribute to pathological sensory processing but suggest a possible role for these neurons in spontaneous pain.
Topics: Action Potentials; Animals; Disease Models, Animal; Humans; Neuralgia; Pain Measurement; Posterior Horn Cells; Spinal Cord Dorsal Horn
PubMed: 31149976
DOI: 10.1097/j.pain.0000000000001632 -
The British Journal of Ophthalmology Nov 2019Compared with current imaging methods, the diagnostic performance and the advantages and limitations of optical coherence tomography angiography (OCTA) remain unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Compared with current imaging methods, the diagnostic performance and the advantages and limitations of optical coherence tomography angiography (OCTA) remain unclear. We performed a systematic review and meta-analysis of studies investigating vessel density (VD) in patients with glaucoma using OCTA.
METHODS
We conducted a literature search on PubMed, Scopus, Web of Science, ISI Conference Proceedings and Google Scholar, along with a manual search, from January 2006 to March 2018. We included prospective studies that used OCTA to compare the VD in glaucomatous eyes with healthy control eyes.
RESULTS
Of 3045 screened articles, 24 were included in a broad characterisation and 18 in the meta-analysis. We observed a statistically significant reduction in the mean peripapillary VD (MPVD) in glaucoma (MPVD: 57.53%, 95% CI 52.60 to 62.46, p< 0.001) compared with controls (MPVD: 65.47%, 95% CI 59.82 to 71.11; standardised mean difference [SMD], -1.41, 95% CI -1.62 to -1.20, p< 0.001) for 888 glaucomatous and 475 healthy eyes, and also in the mean-whole optic nerve image VD (SMD, -9.63, 95% CI -10.22 to -9.03, p<0.001), mean inside-disc VD (SMD, - 9.51, 95% CI -12.66 to -6.36, p<0.05) and mean parafoveal VD (SMD, -3.92, 95% CI -4.73 to -3.12, p<0.001). Subgroup analyses revealed a significant difference in the MPVD across glaucoma subtypes and OCTA devices.
CONCLUSION
This suggests the diagnostic utility of OCTA in detecting glaucomatous eyes; however, further longitudinal prospective studies are welcomed to characterise vascular changes in glaucoma.
Topics: Female; Fluorescein Angiography; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Low Tension Glaucoma; Male; Nerve Fibers; Optic Disk; Prospective Studies; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 30728123
DOI: 10.1136/bjophthalmol-2018-313461 -
Journal of Glaucoma Jun 2016Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a...
PURPOSE
Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a key set of clinical outcomes and reach consensus on how best to measure them from the perspective of glaucoma experts.
METHODS
A 2-round electronic Delphi survey was conducted. Round 1 involved 25 items identified from a systematic review. Round 2 was developed based on information gathered in round 1. A 10-point Likert scale was used to quantify importance and consensus of outcomes (7 outcomes) and ways of measuring them (44 measures). Experts were identified through 2 glaucoma societies membership-the UK and Eire Glaucoma Society and the European Glaucoma Society. A Nominal Group Technique (NGT) followed the Delphi process. Results were analyzed using descriptive statistics.
RESULTS
A total of 65 participants completed round 1 out of 320; of whom 56 completed round 2 (86%). Agreement on the importance of outcomes was reached on 48/51 items (94%). Intraocular pressure (IOP), visual field (VF), safety, and anatomic outcomes were classified as highly important. Regarding methods of measurement of IOP, "mean follow-up IOP" using Goldmann applanation tonometry achieved the highest importance, whereas for evaluating VFs "global index mean deviation/defect (MD)" and "rate of VF progression" were the most important. Retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) was identified as highly important. The NGT results reached consensus on "change of IOP (mean of 3 consecutive measurements taken at fixed time of day) from baseline," change of VF-MD values (3 reliable VFs at baseline and follow-up visit) from baseline, and change of RNFL thickness (2 good quality OCT images) from baseline.
CONCLUSIONS
Consensus was reached among glaucoma experts on how best to measure IOP, VF, and anatomic outcomes in glaucoma randomized controlled trials.
Topics: Delphi Technique; Female; Glaucoma; Humans; Intraocular Pressure; Male; Nerve Fibers; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Surveys and Questionnaires; Tomography, Optical Coherence; Tonometry, Ocular; Visual Fields
PubMed: 26091178
DOI: 10.1097/IJG.0000000000000301 -
FASEB Journal : Official Publication of... Mar 2022Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of...
Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of the most narrowly tuned bitter taste receptors in humans. In this study, we review the literature on this receptor and show there is no consensus about its role. We then compare the possible role of hTAS2R5 with that of the proteins of the TAS2R family in rat, mouse, and pig. A phylogenetic tree of all mammalian TAS2R domain-containing proteins showed that human hTAS2R5 has no ortholog in pig, mouse, or rat genomes. By comparing the agonists that are common to hTAS2R5 and other members of the family, we observed that hTAS2R39 is the receptor that shares most agonists with hTAS2R5. In mouse, some of these agonists activate mTas2r105 and mTas2r144, which are distant paralogs of hTAS2R5. mTas2r144 seems to be the receptor that is most similar to hTAS2R5 because they are both activated by the same agonists and have affinities in the same range of values. Then, we can conclude that hTAS2R5 has a unique functional specificity in humans as it is activated by selective agonists and that its closest functional homolog in mouse is the phylogenetically distant mTas2r144.
Topics: Animals; Genomics; Humans; Phylogeny; Receptors, G-Protein-Coupled; Taste; Taste Buds
PubMed: 35107858
DOI: 10.1096/fj.202101128RR -
Clinical Autonomic Research : Official... Feb 2019Electrochemical skin conductance (ESC) is a non-invasive test of sweat function developed as a potential marker of small fiber neuropathy. Here we systematically review...
OBJECTIVE
Electrochemical skin conductance (ESC) is a non-invasive test of sweat function developed as a potential marker of small fiber neuropathy. Here we systematically review the evolution of this device and the data obtained from studies of ESC across different diseases.
METHODS
Electronic databases, including MEDLINE, and Google Scholar were searched through to February 2018. The search strategy included the following terms: "electrochemical skin conductance," "EZSCAN," and "Sudoscan." The data values provided by each paper were extracted, where available, and input into tabular and figure data for direct comparison.
RESULTS
Thirty-seven studies were included this systematic review. ESC did not change by age or gender, and there was significant variability in ESC values between diseases, some of which exceeded control values. Longitudinal studies of disease demonstrated changes in ESC that were not biologically plausible. Of the 37 studies assessed, 25 received support from the device manufacturer. The extracted data did not agree with other published normative values. Prior studies do not support claims that ESC is a measure of small fiber sensory function or autonomic function.
CONCLUSIONS
Although many papers report significant differences in ESC values between disease and control subjects, the compiled data assessed in this review raises questions about the technique. Many of the published results violate biologic plausibility. A single funding source with a vested interest in the study outcomes has supported most of the studies. Normative values are inconsistent across publications, and large combined data sets do not support a high sensitivity and specificity. Finally, there is insufficient evidence supporting the claim that Sudoscan tests sudomotor or sensory nerve fiber function.
Topics: Animals; Electrochemical Techniques; Galvanic Skin Response; Humans; Sensory Receptor Cells; Skin Physiological Phenomena; Small Fiber Neuropathy; Sweating
PubMed: 29956008
DOI: 10.1007/s10286-018-0540-0 -
European Journal of Translational... Jan 2024The primary aim of this study was to systematically review and meta-analyze the impact of sensorimotor and proprioceptive exercises on balance in older adults. We also...
The primary aim of this study was to systematically review and meta-analyze the impact of sensorimotor and proprioceptive exercises on balance in older adults. We also sought to define how researchers describe proprioceptive and sensory-motor training and their respective protocols. The review was conducted following the PRISMA guidelines, with searches performed in March 2023. Both authors carried out independent searches using the PubMed and PEDro databases. From a total of 320 identified records, 12 studies were deemed eligible for meta-analysis after screening and removal of duplicates. The average PEDro score was 5.11 ± 1.11 indicating overall fair quality of studies. Common outcome measures included the Berg balance scale, Timed up and go test, Tinetti balance scale, Functional reach test and various single-leg stance tests. All outcomes were significantly improved by the interventions (standard mean difference = 0.65 - 1.29), with little difference between proprioceptive and sensorimotor training. However, the quality of evidence ranged from "very low" to "low" based on GRADE guidelines, suggesting further high-quality studies are needed. This review underscores the potential benefits of sensorimotor and proprioceptive exercises for enhancing balance in older adults, while also highlighting the ambiguity and inconsistency regarding the usage of the terms proprioceptive and sensorimotor training.
PubMed: 38213185
DOI: 10.4081/ejtm.2024.12010 -
Retina (Philadelphia, Pa.) Nov 2021To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging.
PURPOSE
To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging.
METHODS
The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions.
RESULTS
A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid.
CONCLUSION
This review serves to strengthen the OCT nomenclature "bacillary layer detachment," based on specific reflectance information obtained by OCT and previously published histologic observations.
Topics: Humans; Retinal Cone Photoreceptor Cells; Retinal Detachment; Retinal Rod Photoreceptor Cells; Terminology as Topic; Tomography, Optical Coherence
PubMed: 34029276
DOI: 10.1097/IAE.0000000000003217