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Frontiers in Neurology 2020The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive...
The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD should be aimed at the pre-dementia clinical stage of AD, i.e., MCI. We aimed to perform a systematic review and meta-analysis on retinal OCT in MCI. We performed a systematic review of the English literature in three databases (PubMed, Embase, and Latindex) for studies that measured retinal thickness using OCT in people with MCI and healthy controls, age 50 or older, between 1 January 2000 and 31 July 2019. Only cohort and case-control studies were reviewed, and independent extraction of quality data and established objective data was performed. We calculated the effect size for studies in the review that met the following criteria: (1) a statistically significant difference between MCI subjects and normal controls for several OCT variables, (2) use of spectral domain OCT, and (3) use of APOSTEL recommendations for OCT reporting. Weighted Hedges' g statistic was used to calculate the pooled effect size for four variables: ( in micrometers (μm), in μm, in μm, and in μm. For variables with high heterogeneity, a multivariate meta-regression was performed. We followed the PRISMA guidelines for systematic reviews. Fifteen articles met the inclusion criteria. A total of 58.9% of MCI patients had statistically significant thinning of the pRNFL compared with normal subjects, while 61.6% of all MCI patients who had macular volume measured had a statistically significant reduction in volume compared with controls, and 50.0% of the macular GCL-IPL complexes measured demonstrated significant thinning in MCI compared with normal controls. Meta-analysis demonstrated a large effect size for decreased macular thickness in MCI subjects compared with normal controls, but there was a substantial heterogeneity for macular thickness results. The other variables did not demonstrate a significant difference and also had substantial heterogeneity. Meta-regression analysis did not reveal an explanation for the heterogeneity. A better understanding of the cause of retina degeneration and longitudinal, standardized studies are needed to determine if optical coherence tomography can be used as a biomarker for mild cognitive impairment due to Alzheimer's disease.
PubMed: 33178120
DOI: 10.3389/fneur.2020.578698 -
Frontiers in Neurology 2020Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated...
Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease. However, the prevalence of AQP4-IgG seropositivity and MOG-IgG seropositivity in isolated ON is unclear, and studies comparing visual outcomes and optical coherence tomography (OCT)-derived structural retinal measures between MS-ON, AQP4-ON, and MOG-ON eyes are limited by small sample sizes. (1) To assess the prevalence of AQP4-IgG and MOG-IgG seropositivity among patients presenting with isolated ON; (2) to compare visual outcomes and OCT measures between AQP4-ON, MOG-ON, and MS-ON eyes. In this systematic review and meta-analysis, a total of 65 eligible studies were identified by PubMed search. Statistical analyses were performed with random effects models. In adults with isolated ON, AQP4-IgG seroprevalence was 4% in non-Asian and 27% in Asian populations, whereas MOG-IgG seroprevalence was 8 and 20%, respectively. In children, AQP4-IgG seroprevalence was 0.4% in non-Asian and 15% in Asian populations, whereas MOG-IgG seroprevalence was 47 and 31%, respectively. AQP4-ON eyes had lower peri-papillary retinal nerve fiber layer (pRNFL; -11.7 μm, 95% CI: -15.2 to -8.3 μm) and macular ganglion cell + inner plexiform layer (GCIPL; -9.0 μm, 95% CI: -12.5 to -5.4 μm) thicknesses compared with MS-ON eyes. Similarly, pRNFL (-11.2 μm, 95% CI: -21.5 to -0.9 μm) and GCIPL (-6.1 μm, 95% CI: -10.8 to -1.3 μm) thicknesses were lower in MOG-ON compared to MS-ON eyes, but did not differ between AQP4-ON and MOG-ON eyes (pRNFL: -1.9 μm, 95% CI: -9.1 to 5.4 μm; GCIPL: -2.6 μm, 95% CI: -8.9 to 3.8 μm). Visual outcomes were worse in AQP4-ON compared to both MOG-ON (mean logMAR difference: 0.60, 95% CI: 0.39 to 0.81) and MS-ON eyes (mean logMAR difference: 0.68, 95% CI: 0.40 to 0.96) but were similar in MOG-ON and MS-ON eyes (mean logMAR difference: 0.04, 95% CI: -0.05 to 0.14). AQP4-IgG- and MOG-IgG-associated disease are important diagnostic considerations in adults presenting with isolated ON, especially in Asian populations. Furthermore, MOG-IgG seroprevalence is especially high in pediatric isolated ON, in both non-Asian and Asian populations. Despite a similar severity of GCIPL and pRNFL thinning in AQP4-ON and MOG-ON, AQP4-ON is associated with markedly worse visual outcomes.
PubMed: 33132999
DOI: 10.3389/fneur.2020.540156 -
Frontiers in Neurology 2020To investigate the application of optical coherence tomography angiography (OCTA) in cerebral small vessel disease (SVD), ischemic stroke and dementia. We conducted a...
To investigate the application of optical coherence tomography angiography (OCTA) in cerebral small vessel disease (SVD), ischemic stroke and dementia. We conducted a systematic search in MEDLINE (from inception) and EMBASE (from 1980) to end 2019 for human studies that measured retinal parameters in cerebral SVD, ischemic stroke, and dementia using OCTA. Fourteen articles ( = 989) provided relevant data. Ten studies included patients with Alzheimer disease (AD) and mild cognitive impairment ( = 679), two investigated pre-symptomatic AD participants ( = 154), and two investigated monogenic SVD patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( = 32) and Fabry disease ( = 124). Methods to reduce bias and risk factor adjustment were poorly reported. Substantial methodological variations between studies precluded a formal meta-analysis. Quantitative measurements revealed significant yet inconclusive changes in foveal avascular zone, perfusion density, and vessel density (VD) in AD, presymptomatic AD, and SVD patients. Two ( = 160) of three studies ( = 192) showed association between decreased VD and increased white matter hyperintensities. In three ( = 297) of seven studies ( = 563), better cognitive function was associated with increased VD. One study ( = 52) suggested increased VD was associated with increased ganglion cell-inner plexiform layer thickness in AD yet with no covariate adjustment. Changes in retinal microvasculature identified using OCTA are associated with monogenic SVD and different stages of AD, but data are limited and partly confounded by methodological differences. Larger studies with risk factors adjustment and more consistent OCTA methods are needed to fully exploit this technology. CRD42020166929.
PubMed: 33013667
DOI: 10.3389/fneur.2020.01009 -
Eye (London, England) Mar 2021The purpose of this study is to systematically review the reported data of normal optical coherence tomography (OCT) results in the paediatric population. A systematic... (Review)
Review
The purpose of this study is to systematically review the reported data of normal optical coherence tomography (OCT) results in the paediatric population. A systematic literature search was performed using the PubMed, Embase, and Web of Science databases, using the keywords "optical coherence tomography"; "normative data" or "healthy eyes"; "children" or "paediatric population". Studies with at least 50 participants were included, irrespective of the OCT equipment employed. We excluded the OCT angiography studies or the studies investigating the choroidal thickness. Seventy-four studies were included in the final analysis and information on study design, number of participants, demographic characteristics, type of OCT equipment, OCT parameters and results was collected. Due to the high variability of OCT instruments and parameters used, a meta-analysis was not feasible. We report the normative values for the peripapillary retinal nerve fibre layer thickness and the macular retinal thickness for each ETDRS quadrant, as provided by the studies included in the present analysis. We also report the influence of ethnicity, age, gender, eye laterality, ISNT rule, spherical equivalent, and axial length on OCT results.
Topics: Child; Choroid; Cross-Sectional Studies; Humans; Refraction, Ocular; Retina; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 32929184
DOI: 10.1038/s41433-020-01177-3 -
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 -
The Cochrane Database of Systematic... Feb 2020Glaucoma is a multi-factorial optic neuropathy characterized by an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glaucoma is a multi-factorial optic neuropathy characterized by an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding atrophy of the optic nerve. Although many treatments are available to manage glaucoma, patients may seek complementary or alternative medicine approaches such as acupuncture to supplement their regular treatment. The underlying plausibility of acupuncture is that disorders related to the flow of Chi (traditional Chinese concept of vital force or energy) can be managed by stimulating relevant points on the body surface.
OBJECTIVES
To assess the effectiveness and safety of acupuncture compared with other treatments, no treatment, or placebo in patients with glaucoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2018, Issue 11); Ovid MEDLINE; Embase.com; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Allied and Complementary Medicine Database (AMED); PubMed; Latin American and Caribbean Literature on Health Sciences (LILACS); ZETOC; the metaRegister of Controlled Trials (mRCT); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and the National Center for Complementary and Alternative Medicine (NCCAM) website. We did not use any language or date restrictions in the search for trials. We last searched electronic databases on November 16, 2018, with the exception of NCCAM, which we last searched on July 14, 2010, and the metaRegister of Controlled Trials (mRCT), which we last searched on January 8, 2013. We handsearched Chinese medical journals at Peking Union Medical College Library in April 2007. We searched the Chinese Acupuncture Trials Register, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), the Chinese Biological Database (CBM), and the China National Knowledge Infrastructure (CNKI). We last searched Chinese electronic databases on November 19, 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which one arm involved acupuncture treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened results, then extracted the data and assessed risk of bias for eligible trials.
MAIN RESULTS
We included three completed trials and one ongoing trial in the 2019 update of this review. The three completed trials, conducted in Taiwan and the United States, included participants with glaucoma or intraocular hypertension. The interventions investigated varied across trials. One trial compared auricular acupressure-a non-standard acupuncture technique-with the sham procedure in 33 patients. Another trial compared transcutaneous electrical nerve stimulation (TENS) with a sham procedure in 82 patients. The third trial compared 12 sessions of acupuncture on eye-points versus on non-eye-points in 22 patients. All three trials were rated at high risk of bias for at least one domain. The certainty of evidence across all outcomes was very low due to high risk of bias in at least one contributing study; substantial clinical heterogeneity and methodological heterogeneity; and imprecision of results. One trial reported change in the visual field from baseline without any between-group comparison. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret. All three trials reported data for estimation of reduction of intraocular pressure (IOP). However, time points of IOP measurement varied. For the trial comparing acupressure to a sham procedure, the difference in IOP reduction (measured in mm Hg) is estimated to be -3.70 (95% confidence interval [CI] -7.11 to -0.29) for the right eye and -4.90 (95% CI -8.08 to -1.72) for the left eye at four weeks, and -1.30 mm Hg (95% CI -4.78 to 2.18) for the right eye and -2.30 mm Hg (95% CI -5.73 to 1.13) for the left eye at eight weeks. For the trial comparing TENS to sham treatment, the difference reduction is estimated to be -2.81 (95% CI -3.8 to -1.84) for the right eye and -2.58 (95% CI -3.36 to -1.80) for the left eye immediately after treatment, -2.93 (95% CI -3.72 to -2.13) for the right eye and -3.56 (95% CI -4.35 to 2.78) for the left eye 30 minutes after treatment, and finally -3.61 (95% CI -4.47 to -2.75) for the right eye and -3.61 (95% -4.47 to -2.74) for the left eye. For the trial that compared acupuncture on eye-points versus non-eye-points, 11 out of 22 (50%) participants did not complete the treatment. One trial reported data for estimation of visual acuity. When acupressure is compared to sham treatment, the difference in uncorrected visual acuity (UCVA, measured in logMAR) is estimated to be -0.01 (95% CI -0.24 to 0.22) for the right eye and -0.04 (95% CI -0.27 to 0.19) for the left eye at four months, and -0.03 logMAR (95% CI -0.27 to 0.21) for the right eye and -0.16 logMAR (95% CI -0.43 to 0.11) for the left eye at eight months. The difference in best corrected visual acuity (BCVA) is estimated to be 0.10 (95% CI -0.06 to 0.26) for the right eye and 0 (95% CI -0.14 to 0.14) for the left eye at four months, and -0.04 logMAR (95% CI -0.09 to 0.17) for the right eye and -0.04 logMAR (95% CI -0.18 to 0.10) for the left eye at eight months. One trial reported progression of optic disc damage or nerve fiber layer loss without any between-group comparison. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret. One trial reported adverse events in two patients (out of 22) who experienced needle sensitivity. However, the study did not report between-group comparisons. Because of the quantity of missing data (50%), we did not calculate a between-group comparison, as the quantitative results are difficult to interpret.
AUTHORS' CONCLUSIONS
At this time, it is impossible to draw reliable conclusions from available data to support the use of acupuncture for treatment of patients with glaucoma. Because of ethical considerations, RCTs comparing acupuncture alone with standard glaucoma treatment or placebo are unlikely to be justified in countries where the standard of care has already been established.
Topics: Acupuncture Therapy; Glaucoma; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Visual Acuity
PubMed: 32032457
DOI: 10.1002/14651858.CD006030.pub4 -
Advances in Therapy Dec 2019Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy...
Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy due to retinal ganglion cell (RGC) loss. It is a maternally inherited (or sporadic) mitochondrial disorder caused primarily by mutations in genes that encode components of respiratory complex (RC)1 in mitochondria. Mitochondrial deficiency of RC1 compromises ATP production and oxidative stress management in RGCs. The most common LHON-causing mutations are 11778G>A, 3460G>A, and 14484T>C point mutations in MT-ND4, MT-ND1, and MT-ND6. The unusually high mitochondrial load of RGCs makes them particularly sensitive to these mutations. Patients with LHON may be prescribed ubiquinone (a component of RC3) or idebenone, a ubiquinone analogue with enhanced bioavailability to act downstream of RC1. The challenge of accessing the inner mitochondrial membrane with gene therapy for LHON, and other mitochondrial diseases, may be overcome by incorporation of a specific mitochondrion-targeting sequence (MTS) that enables allotropic expression of a nucleus-transcribed ND4 transgene. Because LHON penetrance is incomplete among carriers of the aforementioned mutations, identification of environmental factors, such as heavy smoking, that interact with genetics in the phenotypic expression of LHON may be helpful toward preventing or delaying disease development. LHON has become a model for mitochondrial and neurogenerative diseases owing to it having a clearly identified genetic cause and its early onset and rapid progression characteristics. Hence, LHON studies and genetic treatment advances may inform research of other diseases.
Topics: DNA, Mitochondrial; Electron Transport Complex I; Genetic Therapy; Humans; Mutation; Optic Atrophy, Hereditary, Leber; Phenotype; Point Mutation
PubMed: 31605306
DOI: 10.1007/s12325-019-01113-2