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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 -
Clinical Ophthalmology (Auckland, N.Z.) 2018Smartphone fundoscopy is a new option for visualizing the ocular fundus but must be validated before being included in population-based examinations. Our aim was to...
BACKGROUND
Smartphone fundoscopy is a new option for visualizing the ocular fundus but must be validated before being included in population-based examinations. Our aim was to evaluate the quality of fundoscopic images obtained via smartphone and to compare their agreement with retinal camera images or clinical examination.
METHODS
The database for this study included all observational studies with smartphone fundoscopy that have comparative analyses with the gold standard methods.
RESULTS
Out of 121 potentially relevant studies, nine were included in this analysis, comprising a total of 4,219 eyes. Mean age was 56.6 years (SD±8.5). Combined kappa (κ) agreement statistics were equal to 77.77% (95% CI: 70.34%, 83.70%). No heterogeneity was measured by random effects ( =zero).
CONCLUSION
Fundoscopic images obtained by using smartphones have substantial agreement with gold standards for clinical or photographic exams.
PubMed: 30587904
DOI: 10.2147/OPTH.S182022 -
The Journal of Headache and Pain Oct 2017This systematic review summarizes the existing data on headache and pregnancy with a scope on clinical headache phenotypes, treatment of headaches in pregnancy and... (Review)
Review
This systematic review summarizes the existing data on headache and pregnancy with a scope on clinical headache phenotypes, treatment of headaches in pregnancy and effects of headache medications on the child during pregnancy and breastfeeding, headache related complications, and diagnostics of headache in pregnancy. Headache during pregnancy can be both primary and secondary, and in the last case can be a symptom of a life-threatening condition. The most common secondary headaches are stroke, cerebral venous thrombosis, subarachnoid hemorrhage, pituitary tumor, choriocarcinoma, eclampsia, preeclampsia, idiopathic intracranial hypertension, and reversible cerebral vasoconstriction syndrome. Migraine is a risk factor for pregnancy complications, particularly vascular events. Data regarding other primary headache conditions are still scarce. Early diagnostics of the disease manifested by headache is important for mother and fetus life. It is especially important to identify "red flag symptoms" suggesting that headache is a symptom of a serious disease. In order to exclude a secondary headache additional studies can be necessary: electroencephalography, ultrasound of the vessels of the head and neck, brain MRI and MR angiography with contrast ophthalmoscopy and lumbar puncture. During pregnancy and breastfeeding the preferred therapeutic strategy for the treatment of primary headaches should always be a non-pharmacological one. Treatment should not be postponed as an undermanaged headache can lead to stress, sleep deprivation, depression and poor nutritional intake that in turn can have negative consequences for both mother and baby. Therefore, if non-pharmacological interventions seem inadequate, a well-considered choice should be made concerning the use of medication, taking into account all the benefits and possible risks.
Topics: Analgesics; Electroencephalography; Female; Head; Headache; Headache Disorders; Humans; Magnetic Resonance Imaging; Pregnancy; Pregnancy Complications; Pseudotumor Cerebri; Risk Factors
PubMed: 29052046
DOI: 10.1186/s10194-017-0816-0 -
Health Technology Assessment... Apr 2016Natural fluorescence in the eye may be increased or decreased by diseases that affect the retina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO)... (Review)
Review
BACKGROUND
Natural fluorescence in the eye may be increased or decreased by diseases that affect the retina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this 'fundus autofluorescence' (FAF) by illuminating the retina using a specific light 'excitation wavelength'. FAF imaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of the method for diagnosis or monitoring is unclear.
OBJECTIVE
To conduct a systematic review to determine the accuracy of FAF imaging using cSLO for the diagnosis or monitoring of retinal conditions, including monitoring of response to therapy.
DATA SOURCES
Electronic bibliographic databases; scrutiny of reference lists of included studies and relevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trial registries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Medion database of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited to the English language.
REVIEW METHODS
References were screened for relevance using prespecified inclusion criteria to capture a broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-text versions of relevant records were retrieved and screened by one reviewer and checked by a second. Data were extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second. At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer.
RESULTS
Eight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinal conditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using an excitation wavelength of 488 nm was generally high (range 81-100%), but was lower (55% and 32%) in two studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity ranged from 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusive evidence of the diagnostic accuracy of FAF imaging.
LIMITATIONS
No studies on the accuracy of FAF imaging for monitoring the progression of retinal conditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnostic outcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studies the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported how FAF images were interpreted.
CONCLUSIONS
Although already in use in clinical practice, it is unclear whether or not FAF imaging is accurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoring of retinal conditions. Well-designed prospective primary research studies, which conform to the paradigm of diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosis and monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographic atrophy and central serous chorioretinopathy.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014014997.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Choroidal Neovascularization; Diabetic Retinopathy; Humans; Macular Edema; Optical Imaging; Prospective Studies; Retinal Diseases; Technology Assessment, Biomedical
PubMed: 27115052
DOI: 10.3310/hta20310 -
The Cochrane Database of Systematic... Nov 2015The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma.
OBJECTIVES
To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage.
SEARCH METHODS
We searched several databases for this review. The most recent searches were on 19 February 2015.
SELECTION CRITERIA
We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or ECC.
DATA COLLECTION AND ANALYSIS
We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level.
MAIN RESULTS
We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear.Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study.The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio.Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people.Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD ≥ -6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR).
AUTHORS' CONCLUSIONS
The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base.We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data.
Topics: Diagnostic Errors; Glaucoma; Humans; Nerve Fibers; Odds Ratio; Ophthalmoscopy; Optic Disk; Prospective Studies; Retrospective Studies; Scanning Laser Polarimetry; Sensitivity and Specificity; Tomography, Optical Coherence; Visual Field Tests
PubMed: 26618332
DOI: 10.1002/14651858.CD008803.pub2 -
Asia-Pacific Journal of Ophthalmology... 2015This systematic review was performed to estimate the diagnostic accuracy of the confocal scanning laser ophthalmoscopy in diagnosing glaucoma. We did a sensitive... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to estimate the diagnostic accuracy of the confocal scanning laser ophthalmoscopy in diagnosing glaucoma. We did a sensitive electronic search to find relevant studies. Two reviewers independently screened relevant articles and extracted required data about study methods and reported results of sensitivity and specificity. A meta-analysis was conducted for pooling data to compare different editions of the Heidelberg Retina Tomograph (HRT) with one of its alternatives, scanning laser polarimetry (GDx) with the criteria of "visual field defect" and "changes of nerve fiber layer" as the reference standard. We identified 37 evaluations from 28 relevant primary studies. In these studies, 9573 eyes (4883 glaucomatous and 4689 non-glaucomatous) were assessed with regards to the reference standard using one of the HRT editions with or without GDx. Diagnostic odds ratios were 9.35 [95% confidence interval (CI): 7.58-11.53] for HRT, 11.84 (95% CI: 9.97-14.06) for HRT II, 11.86 (95% CI: 9.16-15.35) for HRT III, and 21.33 (95% CI, 13.56-33.55) for GDx. Although GDx was more accurate than HRT, all editions of HRT had acceptable performance in diagnosing glaucomatous eyes with an ophthalmologist's clinical examination as the reference standard.
Topics: Diagnostic Techniques, Ophthalmological; Glaucoma; Humans; Microscopy, Confocal; Ophthalmoscopy; Scanning Laser Polarimetry; Sensitivity and Specificity; Visual Field Tests; Visual Fields
PubMed: 26068611
DOI: 10.1097/APO.0000000000000085 -
Investigative Ophthalmology & Visual... Dec 2008To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG). (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG).
METHODS
Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model.
RESULTS
Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty.
CONCLUSIONS
No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.
Topics: Diagnostic Techniques, Ophthalmological; False Positive Reactions; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ophthalmoscopy; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Tomography; Tonometry, Ocular; Visual Field Tests
PubMed: 18614810
DOI: 10.1167/iovs.07-1501 -
Journal of Neurology, Neurosurgery, and... Jun 2007The objective of this review was to evaluate whether systematic visual training leads to (1) a restitution of the visual field (restoration), (2) an increase in the... (Review)
Review
The objective of this review was to evaluate whether systematic visual training leads to (1) a restitution of the visual field (restoration), (2) an increase in the visual search field size or an improvement in scanning strategies (compensation) and (3) a transfer of training-related improvements in activities of daily living such as reading. To retrieve relevant publications, computer-aided searches of databases (Medline, Embase, Cinahl, Cochrane Central Registers of Controlled Trials) and extensive reference tracing and hand searching were performed. Subsequently, all retrieved and blinded studies were scored on methodological quality. 14 studies were included, 2 randomised controlled trials (RCTs) and 12 within-subject repeated-measures designs (RMD). One of the two RCT studies had good quality. The internal validity of the RMD studies varied from poor to good. Five studies reported a significant effect of the vision restoration therapy (VRT), whereas two studies reported no effect using scanning laser ophthalmoscopy or Goldmann perimetry as outcome measure. All authors of the studies on scanning compensatory therapy (SCT) found a significant effect of up to 30 degrees visual search field, a significant increase in reading speed or decrease in reading errors. It is unclear to what extent patients benefit from restoration therapy in relation to a more efficient scanning strategy which enables them to read faster or to avoid obstacles in a better way. No study has given a satisfactory answer. SCT seems to provide a more successful rehabilitation with more simple and user-friendly training techniques. Validated questionnaires provide the most reliable subjective data to assess the transfer of the relevance of training procedures to activities of daily living of the patient. Hence, SCT is recommended until the effect of the VRT is defined.
Topics: Brain Diseases; Humans; Recovery of Function; Vision Disorders; Visual Fields
PubMed: 17135455
DOI: 10.1136/jnnp.2006.103853 -
BMJ (Clinical Research Ed.) Jul 2005To evaluate the additional value of funduscopy in the routine management of patients with hypertension. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the additional value of funduscopy in the routine management of patients with hypertension.
DESIGN
Systematic review.
PARTICIPANTS
Adults aged 19 or more with hypertensive retinopathy.
DATA SOURCES
Medline, Embase, and the Cochrane Library from 1990.
REVIEW METHODS
Studies were included that assessed hypertensive retinopathy with blinding for blood pressure and cardiovascular risk factors. Studies on observer agreement had to be assessed by two or more observers and expressed as a kappa statistic. Studies on the association between hypertensive retinopathy and hypertensive organ damage were carried out in patients with hypertension. The association between hypertensive retinopathy and cardiovascular risk was carried out in unselected normotensive and hypertensive people without diabetes mellitus.
RESULTS
The assessment of microvascular changes in the retina is limited by large variation between observers. The positive and negative predictive values for the association between hypertensive retinopathy and blood pressure were low (47% to 72% and 32% to 67%, respectively). Associations between retinal microvascular changes and cardiovascular risk were inconsistent, except for retinopathy and stroke. The increased risk of stroke, however, was also present in normotensive people with retinopathy. These studies did not adjust for other indicators of hypertensive organ damage.
CONCLUSION
Evidence is lacking that routine funduscopy is of additional value in the management of hypertensive patients.
Topics: Adult; Aged; Blood Pressure; Cardiovascular Diseases; Diagnostic Tests, Routine; Humans; Hypertension; Microcirculation; Middle Aged; Observer Variation; Ophthalmoscopy; Retinal Diseases; Retinal Vessels; Risk Factors
PubMed: 16002881
DOI: 10.1136/bmj.331.7508.73