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Eye (London, England) Feb 2017Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye... (Review)
Review
Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.
Topics: Animals; Blindness; Disease Models, Animal; Eye; Optic Nerve Injuries; Organ Transplantation; Retina; Tissue Survival
PubMed: 27983731
DOI: 10.1038/eye.2016.272 -
Journal of the Neurological Sciences Nov 2023Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS.
METHODS
We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package.
RESULTS
From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I = 79%, z-score = -1.79, p = 0.073).
CONCLUSION
OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test.
Topics: Humans; Male; Female; Adult; Middle Aged; Multiple Sclerosis; Retinal Ganglion Cells; Tomography, Optical Coherence; Retina; Multiple Sclerosis, Chronic Progressive; Optic Neuritis
PubMed: 37924591
DOI: 10.1016/j.jns.2023.120847 -
PloS One 2023Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in...
PURPOSE
Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients.
METHODS
The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool.
RESULTS
Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude.
CONCLUSION
There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.
Topics: Humans; Middle Aged; Cytidine Diphosphate Choline; Glaucoma, Open-Angle; Intraocular Pressure; Glaucoma; Retinal Ganglion Cells; Blindness
PubMed: 37768938
DOI: 10.1371/journal.pone.0291836 -
Biology Direct Oct 2023The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56... (Meta-Analysis)
Meta-Analysis Review
The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.
Topics: Humans; Glaucoma, Open-Angle; Antihypertensive Agents; Genome-Wide Association Study; Timolol; Genotype
PubMed: 37833756
DOI: 10.1186/s13062-023-00423-4 -
Eye (London, England) Apr 2024Amacrine cells (ACs) are the most structurally and functionally diverse neuron type in the retina. Different ACs have distinct functions, such as neuropeptide secretion... (Review)
Review
Amacrine cells (ACs) are the most structurally and functionally diverse neuron type in the retina. Different ACs have distinct functions, such as neuropeptide secretion and inhibitory connection. Vasoactive intestinal peptide (VIP) -ergic -ACs are retina gamma-aminobutyric acid (GABA) -ergic -ACs that were discovered long ago. They secrete VIP and form connections with bipolar cells (BCs), other ACs, and retinal ganglion cells (RGCs). They have a specific structure, density, distribution, and function. They play an important role in myopia, light stimulated responses, retinal vascular disease and other ocular diseases. Their significance in the study of refractive development and disease is increasing daily. However, a systematic review of the structure and function of retinal VIP-ACs is lacking. We discussed the detailed characteristics of VIP-ACs from every aspect across species and providing systematic knowledge base for future studies. Our review led to the main conclusion that retinal VIP-ACs develop early, and although their morphology and distribution across species are not the same, they have similar functions in a wide range of ocular diseases based on their function of secreting neuropeptides and forming inhibitory connections with other cells.
Topics: Humans; Amacrine Cells; Vasoactive Intestinal Peptide; Retina; Retinal Ganglion Cells; gamma-Aminobutyric Acid
PubMed: 38066110
DOI: 10.1038/s41433-023-02844-x -
Frontiers in Neurology 2017Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with... (Review)
Review
BACKGROUND
Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with MSA only rarely have visual complaints, but recent studies of the retina using optical coherence tomography (OCT) showed atrophy of the peripapillary retinal nerve fiber layer (RNFL) and to a lesser extent the macular ganglion cell layer (GCL) complex.
METHODS
We performed a literature review and meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines for studies published before January 2017, identified through PubMed and databases, which reported OCT-related outcomes in patients with MSA and controls. A random-effects model was constructed.
RESULTS
The meta-analysis search strategy yielded 15 articles of which 7 met the inclusion criteria. The pooled difference in the average thickness of the RNFL was -5.48 μm (95% CI, -6.23 to -4.73; < 0.0001), indicating significant thinning in patients with MSA. The pooled results showed significant thinning in all the specific RNFL quadrants, except in the temporal RNFL quadrant, where the thickness in MSA and controls was similar [pooled difference of 1.11 µm (95% CI, -4.03 to 6.26; = 0.67)]. This pattern of retinal damage suggests that MSA patients have preferential loss of retinal ganglion cells projecting to the magnocellular pathway (M-cells), which are mainly located in the peripheral retina and are not essential for visual acuity. Visual acuity, on the other hand, relies mostly on macular ganglion cells projecting to the parvocellular pathway (P-cells) through the temporal portion of the RNFL, which are relatively spared in MSA patients.
CONCLUSION
The retinal damage in patients with MSA differs from that observed in patients with Parkinson disease (PD). Patients with MSA have more relative preservation of temporal sector of the RNFL and less severe atrophy of the macular GCL complex. We hypothesize that in patients with MSA there is predominant damage of large myelinated optic nerve axons like those originating from the M-cells. These large axons may require higher support from oligodendrocytes. Conversely, in patients with PD, P-cells might be more affected.
PubMed: 28596752
DOI: 10.3389/fneur.2017.00206 -
Molecular Psychiatry Feb 2024Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs).... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension.
METHODS
Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020.
RESULTS
We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs.
DISCUSSION
Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.
Topics: Humans; Tomography, Optical Coherence; Electroretinography; Schizophrenia; Retina; Biomarkers; Male; Adult; Female; Nerve Fibers
PubMed: 38081943
DOI: 10.1038/s41380-023-02340-4 -
Cold Spring Harbor Perspectives in... Jun 2023Blindness due to rod-cone dystrophies is a significant comorbidity and cause of reduced quality of life worldwide. Optogenetics uses adeno-associated viral (AAV) vectors... (Review)
Review
Blindness due to rod-cone dystrophies is a significant comorbidity and cause of reduced quality of life worldwide. Optogenetics uses adeno-associated viral (AAV) vectors to bypass lost photoreceptors and transfect remnant cell populations of the degenerated retina aiming to restore vision via the ectopic expression of opsins. The optogenetic targeting of retinal ganglion cells (RGCs) has been remarkably successful and several studies have advanced to clinical trials over the recent years. The inner retina and specifically ON bipolar cells represent even more appealing targets due to their intrinsically coded tasks in parallel processing and fine-tuning of visual signals before reaching the output: RGCs. However, present success with pursuing inner and outer retinal cells for optogenetic vision restoration is limited by multiple factors, including AAV tropism, promoter specificity, and retinal morphofunctional remodeling. Here we provide a review of the evolution of optogenetics, its greatest challenges, and solutions from bench to bedside.
Topics: Humans; Optogenetics; Inventions; Quality of Life; Retinal Ganglion Cells; Retina; Retinal Degeneration
PubMed: 36376079
DOI: 10.1101/cshperspect.a041304 -
The Cochrane Database of Systematic... Feb 2016Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome.Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown.
OBJECTIVES
The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma.
SEARCH METHODS
We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest.
MAIN RESULTS
We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting.Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression.One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI -6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI -0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes.Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low.Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy.
AUTHORS' CONCLUSIONS
We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma).
Topics: Aluminum; Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Laser Therapy; Ophthalmologic Surgical Procedures; Randomized Controlled Trials as Topic; Visual Acuity; Yttrium
PubMed: 26871761
DOI: 10.1002/14651858.CD005655.pub2 -
Survey of Ophthalmology 2022Studies reporting alteration in retinal thickness using optical coherence tomography (OCT) have been performed in different populations with various degrees of... (Meta-Analysis)
Meta-Analysis Review
Studies reporting alteration in retinal thickness using optical coherence tomography (OCT) have been performed in different populations with various degrees of refractive error, producing inconsistent results. Therefore, we performed a meta-analysis to evaluate the alterations in retinal OCT measurements in myopic and hyperopic patients compared to controls. Evaluation of different retinal layers' thickness may have significance for developing novel approaches for preventing, diagnosing, and treating refractive errors and their complications. We searched PubMed and EMBASE to identify articles that reported OCT measurements of different retinal layers and regions, including macular, foveal, parafoveal, perifoveal, foveolar, ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell and inner plexiform layer (GC-IPL) thickness in addition to macular volume, and optic disc area in myopes and hyperopes comparing their differences with controls. We applied either a fixed-effects or random-effects model for the meta-analysis of these differences based on the assessed heterogeneity level. Furthermore, subgroup analyses and metaregression, as well as publication bias and quality assessment, were conducted for the eligible studies. Forty-seven studies with a total of 12223 eyes, including 8600 cases and 3623 non-cases, are included in this meta-analysis. Our results showed that, in comparison to controls, highly myopic eyes had a significantly lower value for mean macular thickness, macular GCC, macular GC-IPL, parafoveal, perifoveal, foveal, foveolar, RNFL, and pRNFL thickness. Compared to controls, moderately myopic eyes showed a significantly thinner mean macular GCC layer and pRNFL. On the other hand, hyperopic eyes had significantly thicker average pRNFL than controls. Several other significant differences were also observed in various regional analyses. The findings of the current study affirm the retinal OCT measurement differences between myopic and hyperopic eyes compared to controls, emphasizing OCT measurements' advantages as potential biomarkers of ocular pathologies.
Topics: Humans; Nerve Fibers; Optic Disk; Refractive Errors; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 34343537
DOI: 10.1016/j.survophthal.2021.07.007