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Biomedicine & Pharmacotherapy =... Nov 2023Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support... (Review)
Review
Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support and maintenance of the retinal pigment epithelium (RPE). In subretinal hemorrhage (SRH), blood accumulates between the neurosensory retina and the RPE or between the RPE and the choroid. Blood breakdown products subsequently damage PRs and the RPE and lead to poor vision and blindness. Hence, there is a high need for options to preserve the retina and visual functions. We conducted a systematic review of the literature in accordance with the PRISMA guidelines to identify the cell death mechanisms in RPE and PRs after SRH to deepen our understanding of the pathways involved. After screening 736 publications published until November 8, 2022, we identified 19 records that assessed cell death in PRs and/or RPE in experimental models of SRH. Among the different cell death mechanisms, apoptosis was the most widely investigated mechanism (11 records), followed by ferroptosis (4), whereas necroptosis, pyroptosis, and lysosome-dependent cell death were only assessed in one study each. We discuss different therapeutic options that were assessed in these studies, including the removal of the hematoma/iron chelation, cytoprotection, anti-inflammatory agents, and antioxidants. Further systematic investigations will be necessary to determine the exact cell death mechanisms after SRH with respect to different blood breakdown components, cell types, and time courses. This will form the basis for the development of novel treatment options for SRH.
Topics: Humans; Retinal Pigment Epithelium; Retina; Cell Death; Photoreceptor Cells; Hemorrhage
PubMed: 37742603
DOI: 10.1016/j.biopha.2023.115572 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of... (Review)
Review
Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) as a Screening Marker for Familial Adenomatous Polyposis (FAP): Systematic Literature Review and Screening Recommendations.
PURPOSE
Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a highly specific phenotypical marker for FAP that can be used in screening at-risk individuals. Screening recommendations including morphological subclassification were formulated with supporting literature.
METHODS
A systematic literature review with a comprehensive search strategy was conducted using online databases. Manual searches of bibliographies and reference lists were also performed. Studies meeting inclusion criteria were graded with respect to their hierarchy of evidence and strength of recommendations according to the National Health and Medical Research Council (NHMRC) guidelines of Australia.
RESULTS
Almost 4500 participants were analysed across 28 included studies. The mean specificity of CHRPE as a phenotypical screening marker of FAP was 89% (standard deviation (SD); 14) with a mean sensitivity of 79% (SD; 8). The mean prevalence of CHRPE amongst FAP participants; at-risk participants were found to be 76% (SD; 24) and 37% (SD; 21) respectively. Bilateralism and multiple lesion number ≥3 are features highly specific for FAP.
CONCLUSION
CHRPE was found to be a non-invasive, rapid, early phenotypical screening marker of FAP. Clinical recognition further allows increased gene analysis efficiency. The absence of CHRPE alone cannot exclude FAP. Our screening recommendations provide guidance to clinicians on evidence based CHRPE assessment. We would advocate inclusion of ocular examinations as part of a three-pronged approach, along with endoscopy and genetic testing, for efficient, timely FAP assessment in at-risk individuals.
PubMed: 35321042
DOI: 10.2147/OPTH.S354761 -
BMC Ophthalmology Nov 2023To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.
OBJECTIVES
To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED).
METHODS
Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022.
RESULTS
One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58.
CONCLUSIONS
IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Retinal Detachment; Network Meta-Analysis; Vascular Endothelial Growth Factor A; Retinal Pigment Epithelium; Retrospective Studies; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Intravitreal Injections; Macular Degeneration
PubMed: 37990182
DOI: 10.1186/s12886-023-03214-7 -
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 -
Advances in Therapy Mar 2022Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss... (Review)
Review
INTRODUCTION
Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited.
METHODS
Medline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients.
RESULTS
A total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20-2.37 and 11.09-26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between ~ 2-16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26-16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2-14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1-3% of RP and 0.8-3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81-8% in the Middle East region.
CONCLUSIONS
There are significant variations in reporting of RPE65 proportions within countries as well as regions. Generating robust epidemiological evidence on RPE65 gene-mediated IRDs would be fundamental to support rare disease awareness, timely therapeutic intervention, and public health decision-making.
Topics: Adult; Child; Humans; Leber Congenital Amaurosis; Mutation; Retinal Dystrophies; Retinal Pigment Epithelium; cis-trans-Isomerases
PubMed: 35098484
DOI: 10.1007/s12325-021-02036-7 -
The Cochrane Database of Systematic... Sep 2014Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the... (Review)
Review
BACKGROUND
Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these lesions frequently is recommended, in spite of the fact that the effectiveness of this therapy is unproven.
OBJECTIVES
The objective of this review was to assess the effectiveness and safety of techniques used to treat asymptomatic retinal breaks and lattice degeneration for the prevention of retinal detachment.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), PubMed (January 1948 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), 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 19 February 2014. Textbooks regarding retinal detachment and the reference lists of relevant reports were reviewed for additional study reports. We contacted experts in the field for details of other published and unpublished studies.
SELECTION CRITERIA
This review was designed to include randomized controlled trials in which one treatment for asymptomatic retinal breaks and lattice degeneration was compared with another treatment or no treatment.
DATA COLLECTION AND ANALYSIS
Initially, one author assessed the search results and collected relevant studies. Since no studies met the inclusion criteria, no studies were assessed for risk of bias. No data were extracted and no meta-analysis could be performed.
MAIN RESULTS
No trials were found that met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
No conclusions could be reached about the effectiveness of surgical interventions to prevent retinal detachment in eyes with asymptomatic retinal breaks or lattice degeneration, or both. Current recommendations for treatment, based upon a consensus of expert opinion, should be assessed in a randomized controlled trial.
Topics: Humans; Retinal Degeneration; Retinal Detachment; Retinal Perforations
PubMed: 25191970
DOI: 10.1002/14651858.CD003170.pub4 -
BMJ Clinical Evidence Apr 2007Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with... (Review)
Review
INTRODUCTION
Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early-stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression of early- or late-stage age-related macular degeneration; and exudative age-related macular degeneration? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiangiogenesis (using pegaptanib, ranibizumab, interferon alfa-2a, or anecortave acetate), antioxidant vitamins plus zinc, external beam radiation, laser treatment to drusen, photodynamic therapy with verteporfin, submacular surgery, thermal laser photocoagulation, transpupillary thermotherapy.
Topics: Choroidal Neovascularization; Humans; Macular Degeneration; Photochemotherapy; Ranibizumab; Visual Acuity
PubMed: 19454069
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2012Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the... (Review)
Review
BACKGROUND
Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these problems is frequently recommended, in spite of the fact that the effectiveness of this therapy is unproven.
OBJECTIVES
The purpose of this review was to evaluate the effectiveness of interventions for asymptomatic retinal breaks and lattice degeneration.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 28 January 2012. Textbooks regarding retinal detachment and the reference lists of relevant reports were reviewed for additional study reports. Experts in the field were contacted for details of other published and unpublished studies.
SELECTION CRITERIA
This review was designed to include randomized controlled trials in which one treatment for asymptomatic retinal breaks and lattice degeneration was compared to another treatment or to no treatment.
DATA COLLECTION AND ANALYSIS
Initially one author assessed the search results and collected relevant studies. Since no studies met the inclusion criteria, no studies were assessed for methodological quality. No data were extracted and no meta-analysis could be performed.
MAIN RESULTS
No trials were found that met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
No conclusions could be reached about the effectiveness of surgical interventions to prevent retinal detachment in eyes with asymptomatic retinal breaks and/or lattice degeneration. Some current recommendations for treatment, based upon a consensus of expert opinion, are contradicted by the best available evidence.
Topics: Humans; Retinal Degeneration; Retinal Detachment; Retinal Perforations
PubMed: 22419286
DOI: 10.1002/14651858.CD003170.pub3 -
Antioxidants (Basel, Switzerland) Aug 2021Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses... (Review)
Review
Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue. The aim of this systematic review is to examine the neuroprotective potential of the xanthophyll carotenoids lutein, zeaxanthin, and -zeaxanthin on retinal neurodegeneration for the purpose of adjunctive nutraceutical strategy in the management of AMD. A comprehensive literature review was performed to retrieve 55 eligible publications, using four database searches from PubMed, Embase, Cochrane Library, and the Web of Science. Epidemiology studies indicated an enhanced risk reduction against late AMD with greater dietary consumption of carotenoids, meanwhile greater concentrations in macular pigment demonstrated significant improvements in visual function among AMD patients. Collectively, evidence strongly suggests that carotenoid vitamin therapies offer remarkable synergic protection in the neurosensory retina, with the potential to serve as adjunctive nutraceutical therapy in the management of established AMD, albeit these benefits may vary among different stages of disease.
PubMed: 34439503
DOI: 10.3390/antiox10081255 -
Current Journal of Neurology Jan 2023This study was conducted to evaluate the relationship between retinal layer thickness (RLT) and cognition in patients with multiple sclerosis (MS). We searched PubMed,... (Review)
Review
This study was conducted to evaluate the relationship between retinal layer thickness (RLT) and cognition in patients with multiple sclerosis (MS). We searched PubMed, Scopus, Embase, Web of Science, and Google Scholar. The search strategy included the MeSH and text words as ["ora serrata" OR "retina" OR ("coherence tomography" AND "optical") OR "OCT tomography" OR (tomography AND OCT) OR "optical coherence tomography" OR "OCT" OR "retinal thickness" OR "inner plexiform layer" OR "nerve fiber layer" OR "ganglion cell layer" OR "inner nuclear layer" OR "outer plexiform layer" OR "outer nuclear layer" OR "external limiting membrane" OR "inner segment layer" OR "outer segment layer" OR "retinal pigment epithelium"] AND ["cognition"* OR "cognitive function"* OR (function* AND cognitive)] AND [(sclerosis AND multiple) OR (sclerosis AND disseminated) OR "disseminated sclerosis" OR "multiple sclerosis" OR "acute fulminating"]. The literature search revealed 1090 articles; after deleting duplicates, 980 remained. Finally, 14 studies were included. Totally, 1081 patients were evaluated. Mean age ranged from 31 to 55 years. In some studies, there was a correlation between cognition and retinal thickness, while others did not confirm this finding. Some authors found cognitive impairment (CI) in patients with MS with RLT. The results of this systematic review show that there are discrepancies between the results of studies regarding the relationship between RLT and cognition status in patients with MS. Further studies with more included original studies and meta-analysis are recommended.
PubMed: 38011353
DOI: 10.18502/cjn.v22i1.12617