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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 -
Ophthalmology Apr 2019OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD)... (Meta-Analysis)
Meta-Analysis
TOPIC
OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI.
CLINICAL RELEVANCE
Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD.
METHODS
We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell-inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality.
RESULTS
We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence interval [CI], -0.80 to -0.11; I = 71%), GCC thickness (SMD, -0.84; 95% CI, -1.10 to -0.57; I = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I = 80%), and macular thickness of all inner and outer sectors (SMD range, -0.52 to -0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, -0.67; 95% CI, -0.95 to -0.38; I = 89%) and choroidal thickness (SMD range, -0.88 to -1.03; all P < 0.001) also were thinner in AD patients.
CONCLUSIONS
Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD.
Topics: Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Nerve Fibers; Organ Size; Retina; Retinal Diseases; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 30114417
DOI: 10.1016/j.ophtha.2018.08.009 -
Chronic Respiratory Disease Aug 2017Patients with chronic obstructive pulmonary disease (COPD) show several extrapulmonary abnormalities such as impairment in the autonomic function (AF). Similarly, the... (Review)
Review
Patients with chronic obstructive pulmonary disease (COPD) show several extrapulmonary abnormalities such as impairment in the autonomic function (AF). Similarly, the use of respiratory training techniques such as controlled breathing techniques, noninvasive mechanical ventilation (NIMV), and oxygen supplementation for AF modulation in patients with COPD is popular in existing literature. However, the evidence to support their use is nonexistent. A systematic search of studies reporting on the effect of controlled breathing techniques, NIMV, and/or oxygen supplementation techniques on AF outcome parameters was conducted in three online databases: PubMed, Embase, and Web of Science. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, relevant studies were retained and qualitatively analyzed for evidence synthesis. The methodological quality in these studies was evaluated using the evidence based guideline development (EBRO) checklists per designs provided by the Dutch Cochrane Centre. Eighteen studies met the inclusion criteria of the review and were included and discussed. The evidence synthesis revealed that a strong and moderate level evidence supported oxygen supplementation and slow breathing techniques, respectively, in significantly enhancing the baroreceptor sensitivity (BRS) values in patients with COPD. The effect of the examined techniques on the heart rate variability and muscle sympathetic nerve activity was of a limited or inconsistent evidence. The findings from this review suggest that oxygen supplementation and controlled breathing techniques have profound positive influence on the BRS in patients with COPD. However, it is not fully clear whether these influence translates to any therapeutic benefit on the general AF of patients with COPD in the long term.
Topics: Breathing Exercises; Heart Rate; Humans; Noninvasive Ventilation; Oxygen Inhalation Therapy; Pressoreceptors; Pulmonary Disease, Chronic Obstructive; Sympathetic Nervous System
PubMed: 28774205
DOI: 10.1177/1479972316680844 -
Brazilian Journal of Otorhinolaryngology 2017The natural aging process may result in morphological changes in the vestibular system and in the afferent neural pathway, including loss of hair cells, decreased... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The natural aging process may result in morphological changes in the vestibular system and in the afferent neural pathway, including loss of hair cells, decreased numbers of vestibular nerve cells, and loss of neurons in the vestibular nucleus. Thus, with advancing age, there should be a decrease in amplitudes and an increase in latencies of the vestibular evoked myogenic potentials, especially the prolongation of p13 latency. Moreover, many investigations have found no significant differences in latencies with advancing age.
OBJECTIVE
To determine if there are significant differences in the latencies of cervical and ocular evoked myogenic potentials between elderly and adult patients.
METHODS
This is a systematic review with meta-analysis of observational studies, comparing the differences of these parameters between elderly and young adults, without language or date restrictions, in the following databases: Pubmed, ScienceDirect, SCOPUS, Web of Science, SciELO and LILACS, in addition to the gray literature databases: OpenGrey.eu and DissOnline, as well as Research Gate.
RESULTS
The n1 oVEMP latencies had a mean delay in the elderly of 2.32ms with 95% CI of 0.55-4.10ms. The overall effect test showed p=0.01, disclosing that such difference was significant. The heterogeneity found was I=96% (p<0.001). Evaluation of p1 latency was not possible due to the low number of articles selected for this condition. cVEMP analysis was performed in 13 articles. For the p13 component, the mean latency delay in the elderly was 1.34ms with 95% CI of 0.56-2.11ms. The overall effect test showed a p<0.001, with heterogeneity value I=92% (p<0.001). For the n23 component, the mean latency delay for the elderly was 2.82ms with 95% CI of 0.33-5.30ms. The overall effect test showed p=0.03. The heterogeneity found was I=99% (p<0.001).
CONCLUSION
The latency of oVEMP n1 wave component and latencies of cVEMP p13 and n23 wave components are longer in the elderly aged >60 years than in young adults.
Topics: Aged; Aging; Humans; Reaction Time; Vestibular Evoked Myogenic Potentials
PubMed: 28237301
DOI: 10.1016/j.bjorl.2016.12.006 -
The Cochrane Database of Systematic... Jan 2017Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field... (Review)
Review
BACKGROUND
Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death.
OBJECTIVES
The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until study investigators provide additional study details. We documented reasons for excluding studies from the review.
MAIN RESULTS
We included one multicenter RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was progression of visual field loss after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, the investigators excluded 12 (6.3%) after randomization; 77 participants (40.5%) did not complete four years of follow-up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%).Of those remaining in the study at four years, participants assigned to brimonidine showed less progression of visual field loss than participants assigned to timolol (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.14 to 0.86; 101 participants). Because of high risk of attrition bias and potential selective outcome reporting, we graded the certainty of evidence for this outcome as very low. At the four-year follow-up, the mean IOP was similar in both groups among those for whom data were available (mean difference 0.20 mmHg, 95% CI -0.73 to 1.13; 91 participants; very low-certainty evidence). The study authors did not report analyzable data for visual acuity or any data related to vertical cup-disc ratio, quality of life, or economic outcomes. The most frequent adverse event was ocular allergy to the study drug, which affected more participants in the brimonidine group than the timolol group (RR 5.32, 95% CI 1.64 to 17.26; 178 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Although the only trial we included in this review found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that we can draw no conclusions from this finding. Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG. Such research should focus on outcomes important to patients, such as preservation of vision, and how these outcomes relate to cell death and optic nerve damage. As OAG is a chronic, progressive disease with variability in symptoms, RCTs designed to measure the effectiveness of neuroprotective agents require a long-term follow-up of five years or longer to detect clinically meaningful effects.
Topics: Adult; Antihypertensive Agents; Brimonidine Tartrate; Disease Progression; Glaucoma, Open-Angle; Humans; Neuroprotective Agents; Optic Nerve; Optic Nerve Diseases; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Timolol
PubMed: 28122126
DOI: 10.1002/14651858.CD006539.pub4 -
Acta Ophthalmologica Mar 2018To evaluate the role of neural integrators (NI) in the oculomotor system. (Review)
Review
PURPOSE
To evaluate the role of neural integrators (NI) in the oculomotor system.
METHODS
A literature search was carried out using several electronic databases during the months of June 2014 to March 2015. The following keywords were used to generate focused results: 'neural integrators', 'gaze-holding', 'oculomotor integration', 'impaired gaze-holding', 'gaze evoked nystagmus' and 'gaze dysfunction'. Further materials were found through searching relevant articles within reference lists. Seventy-one articles were sourced for this review which analysed animal and human subjects and network models; 45 were studies of humans, 16 studies of primates, three studies of felines and one study from rats and network models. The remaining articles were literature reviews.
RESULTS
The horizontal and vertical, including torsional, NI are located logically in the brainstem, nearby their appropriate target extraocular motoneuron nuclei for stable eye position in eccentric position. The nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are closely linked at the caudal pons and dorsal rostral medulla, integrating horizontal conjugate eye movement. The interstitial nucleus of Cajal (INC) integrates vertical and torsional eye movement at the upper midbrain. The integrator time constant is averaged to 25 seconds in human horizontal and animal vertical NI to perform its function. Case reports revealed that dysfunction of horizontal NI also resulted in vertical ocular deviations, indicating some overlap of horizontal and vertical gaze control. Furthermore, pharmacological inactivation of NI exposed a population of inhibitory neurotransmitters that permits its mechanism of action; allowing for smooth conjugate movement.
CONCLUSIONS
Neural integrators operate to integrate eye velocity and eye position information to provide signals to extraocular motoneurons to attain and maintain a new position. Therefore, NI allow image stabilization during horizontal and vertical eye movements at eccentric positions for comfortable single vision.
Topics: Animals; Eye Movements; Fixation, Ocular; Humans; Oculomotor Nerve; Sensory Receptor Cells; Visual Fields
PubMed: 27874249
DOI: 10.1111/aos.13307 -
Respiratory Care Dec 2015Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and... (Review)
Review
Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Circadian Rhythm; Heart Rate; Humans; Motor Activity; Muscles; Pressoreceptors; Pulmonary Disease, Chronic Obstructive
PubMed: 26487747
DOI: 10.4187/respcare.04174 -
Pain Physician 2015Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings are more related to age than to a patient's symptoms. Besides its common occurrence, chronic idiopathic neck pain is also very disabling with almost 50% of all neck pain patients showing moderate disability at long-term follow-up. Central sensitization (CS) is defined as "an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity," "increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input," or "an augmentation of responsiveness of central neurons to input from unimodal and polymodal receptors." There is increasing evidence for involvement of CS in many chronic pain conditions. Within the area of chronic idiopathic neck pain, there is consistent evidence for the presence and clinical importance of CS in patients with traumatic neck pain, or whiplash-associated disorders. However, the majority of chronic idiopathic neck pain patients are unrelated to a traumatic injury, and hence are termed chronic idiopathic non-traumatic neck pain. When comparing whiplash with idiopathic non-traumatic neck pain, indications for different underlying mechanisms are found.
OBJECTIVE
The goal of this article was to review the existing scientific literature on the role of CS in patients with chronic idiopathic non-traumatic neck pain.
STUDY DESIGN
Systematic review.
SETTING
All selected studies were case control studies.
METHODS
A systematic search of existing, relevant literature was performed via the electronic databases Medline, Embase, Web of Science, Cinahl, PubMed, and Google Scholar. All titles and abstracts were checked to identify relevant articles. An article was considered eligible if it met following inclusion criteria: (1) participants had to be human adults (> 18 years) diagnosed with idiopathic non-traumatic chronic (present for at least 3 months) neck pain; (2) papers had to report outcomes related to CS; and (3) articles had to be full-text reports or original research (no abstracts, case-reports, reviews, meta-analysis, letters, or editorials).
RESULTS
Six articles were found eligible after screening the title, abstract and - when necessary - the full text for in- and exclusion criteria. All selected studies were case-control studies. Overall, results regarding the presence of CS were divergent. While the majority of patients with chronic traumatic neck pain (i.e. whiplash) are characterized by CS, this is not the case for patients with chronic idiopathic neck pain. The available evidence suggests that CS is not a major feature of chronic idiopathic neck pain. Individual cases might have CS pain, but further work should reveal how they can be characterized.
LIMITATIONS
Very few studies available.
CONCLUSIONS
Literature about CS in patients with chronic idiopathic non-traumatic neck pain is rare and results from the available studies provide an inconclusive message. CS is not a characteristic feature of chronic idiopathic and non-traumatic neck pain, but can be present in some individuals of the population. In the future a subgroup with CS might be defined, but based on current knowledge it is not possible to characterize this subgroup. Such information is important in order to provide targeted treatment.
Topics: Adult; Central Nervous System Sensitization; Chronic Disease; Chronic Pain; Female; Humans; Male; Middle Aged; Neck Pain; Whiplash Injuries
PubMed: 26000666
DOI: No ID Found