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Acta Ophthalmologica Feb 2022Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these... (Meta-Analysis)
Meta-Analysis
Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetic Retinopathy; Humans; Inflammation; Macular Edema; Vitreous Body
PubMed: 33945678
DOI: 10.1111/aos.14891 -
Survey of Ophthalmology 2022Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's... (Meta-Analysis)
Meta-Analysis Review
Ocriplasmin for treatment of vitreomacular traction and macular hole: A systematic literature review and individual participant data meta-analysis of randomized, controlled, double-masked trials.
Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.
Topics: Female; Fibrinolysin; Humans; Intravitreal Injections; Peptide Fragments; Retinal Diseases; Retinal Perforations; Tomography, Optical Coherence; Traction; Treatment Outcome; Vision Disorders; Visual Acuity; Vitreous Body; Vitreous Detachment
PubMed: 34480895
DOI: 10.1016/j.survophthal.2021.08.003 -
BMC Ophthalmology Nov 2023Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.
METHODS
A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.
RESULTS
The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).
CONCLUSION
The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.
TRIAL REGISTRATION
CRD42023400305.
Topics: Humans; Methotrexate; Retinal Neoplasms; Prospective Studies; Vitreous Body; Central Nervous System Neoplasms; Lymphoma
PubMed: 37993841
DOI: 10.1186/s12886-023-03226-3 -
Acta Ophthalmologica Mar 2021Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and... (Meta-Analysis)
Meta-Analysis
Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and predictive biomarkers. Given the heterogeneity of data within the literature, we aimed to quantitatively summarize data related to inflammatory cytokines in nAMD. A systematic search without year limitation was performed up to 13 April 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with nAMD. Data were extracted from 95 studies that encompassed 3105 study eyes with nAMD and 1209 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with nAMD and controls. Among the 4314 eyes in 95 studies, aqueous concentrations (standard mean difference, 95% confidence interval and p-value) of MCP-1 (0.43, 0.09 to 0.77 and p = 0.01), MIG (0.63, 0.31 to 0.94 and p = 0.0001), TGF-β (0.45, 0.07 to 0.82 and p = 0.02) and VEGF (0.64, 0.31 to 0.98 and p = 0.0001) were significantly higher in patients with nAMD compared to healthy controls. No differences, failed sensitivity analyses or insufficient data were found between patients with nAMD and healthy controls for the concentrations of the remaining cytokines and with all vitreous samples. Previous studies had shown conflicting associations with nAMD for all 27 cytokines assessed. Our analysis indicates multiple candidate cytokines other than VEGF that are implicated in nAMD and adds clarity to the previous literature. This will help focus translational research in nAMD investigating biomarkers and therapeutic targets.
Topics: Aqueous Humor; Biomarkers; Cytokines; Humans; Inflammation; Vitreous Body; Wet Macular Degeneration
PubMed: 32602185
DOI: 10.1111/aos.14537 -
Forensic Science International Jan 2020Body fluid analysis has played a crucial role in ascertaining various characteristics and has greatly aided in reconstructing events during crime scene investigation. It...
Body fluid analysis has played a crucial role in ascertaining various characteristics and has greatly aided in reconstructing events during crime scene investigation. It is often presumed that crimes that involve violence and mental disturbances such as murder or sexual assault provide good sources of body fluids such as blood, saliva, semen, vaginal secretions, urine and tears. Tears are secreted in response to any emotional or stressful situations and may be found deposited on surfaces such as bedding, tissue paper or cloth. In the absence of the commonly noted body fluids such as blood or saliva, tears can play an important role that can lead to personal identification by examining the biochemistry and molecular aspects to obtain a full DNA profile. Additionally, identification of an individual may be done by carefully observing certain unique eye characteristics such as heterochromia which is highly individualistic. Characteristics of eyewear such as spectacles and contact lenses have unique properties and prescription criteria for correcting an individual's eyesight that can provide vital clues in understanding the visual ability of an individual. In crime scene investigation, the presence or absence of eyewear provides immense evidentiary value that has greatly aided in solving cases such as Janet Abaroa's Murder. This paper provides a systematic review of the possibility of using tears and eyewear for the purpose of forensic investigation and to statistically support the inferences with prescription databases which may be initiated across different populations. Forensic Optometry is yet to get streamlined along with the routinely followed investigative techniques and scientifically explored although no standard protocols exist to analyse eyewear. The use of behavioural optometry is gaining attention in the context of driving laws of different countries and is a simple but powerful indicator of abnormal behaviour. It is speculated that the last seen image referred to as an 'Optogram' of an individual may be captured in the retina since our eyes functions like a camera. Although this claim is considerably unexplored, it is quite possible that the last seen image of a criminal, objects or a place may be noted that can positively help in linking individuals at the scene of crime or identify the primary crime location. In this review, the potential for new insights into the analysis of tears, eye and eyewear characteristics have been explored.
Topics: Contact Lenses; DNA; DNA Fingerprinting; Databases, Factual; Epithelium, Corneal; Eye; Eye Movements; Eyeglasses; Forensic Sciences; Humans; Postmortem Changes; Prescriptions; Specimen Handling; Substance-Related Disorders; Tears; Vitreous Body
PubMed: 31785512
DOI: 10.1016/j.forsciint.2019.110055 -
Acta Ophthalmologica Jun 2019Flashes and floaters are the hallmark symptoms of a posterior vitreous detachment (PVD) which itself is related to an increased risk of the development of retinal tears,...
Flashes and floaters are the hallmark symptoms of a posterior vitreous detachment (PVD) which itself is related to an increased risk of the development of retinal tears, retinal detachment and vitreous haemorrhage. The aim of this study is to assess the associations between different symptoms related to PVD and the risk of developing retinal tears. A systematic review of articles written in English, using MEDLINE, Embase (via Embase.com) and the Cochrane Controlled Trials Register (1996-2017) was conducted. Search terms included five elements: PVD, retinal tears, retinal detachment, floaters and flashes. Independent extraction of articles was conducted by two authors using predefined data fields, including study quality indicators. Thirteen studies fulfilled the selection criteria. Analysis of pooled data revealed that presence of isolated flashes was associated with the development of retinal tears in 5.3% of symptomatic eyes [mean 2.9 eyes; 95% CI (2.1, 5.7)].Conversely, floaters alone had a stronger association with retinal tears (16.5% of eyes), as compared to flashes. The association to retinal tears was even greater for those patients reporting both flashes and floaters [mean 17.8 eyes (20.0%); 95% CI (17.4, 18.1)]. Retinal and/or vitreous haemorrhage was also associated with the presence and later development of retinal tears [mean 12.5 eyes (30.0%); 95% CI (11.7, 13.9)]. Patients with more than 10 floaters or a cloud in their vision had a high risk of developing retinal tears (OR19.8, p-value 0.032). In the setting of a PVD, the onset of flashes and floaters, and the presence of retinal and/or vitreous haemorrhage are risk factors for the development of retinal tears. The association is greater when both symptoms are present, and even greater when the patient reports more than 10 floaters, a curtain or a cloud and/or there is a positive finding of a vitreous or retinal haemorrhage. This study supports the necessity of an immediate examination of patients presenting with symptoms related to a PVD, and a follow-up examination might be prudent in a subgroup of these patients.
Topics: Fluorescein Angiography; Fundus Oculi; Global Health; Humans; Incidence; Retina; Retinal Perforations; Risk Assessment; Risk Factors; Vitreous Body; Vitreous Detachment
PubMed: 30632695
DOI: 10.1111/aos.14012 -
Eye (London, England) Jul 2023
Meta-Analysis
Topics: Humans; Cytokines; Diabetic Retinopathy; Vitreous Body; Vitrectomy; Diabetes Mellitus
PubMed: 36310184
DOI: 10.1038/s41433-022-02294-x -
Survey of Ophthalmology 2024Primary vitreoretinal lymphoma is a potentially aggressive intraocular malignancy with poor systemic prognosis and sometimes significant diagnostic delays as it may... (Review)
Review
Primary vitreoretinal lymphoma is a potentially aggressive intraocular malignancy with poor systemic prognosis and sometimes significant diagnostic delays as it may masquerade as chronic uveitis. Despite the variety of diagnostic techniques, it is unclear which modality is most accurate in the diagnosis of PVRL. A systematic literature search was conducted on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials for studies published between January, 2000, and June, 2023. Randomized controlled trials (RCTs) reporting on the following diagnostic tools used to diagnose patients with PVRL were included: cytology, flow cytometry, MYD88 L265P mutation, CD79B mutation, interleukin 10/interleukin-6 (IL-10/IL-6) ratio, polymerase chain reaction (PCR) for monoclonal immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (IgK) rearrangements, and imaging findings. The aggregated sensitivity of each diagnostic modality was reported and compared using the chi-squared (χ2) test. A total of 662 eyes from 29 retrospective studies reporting on patients diagnosed with PVRL were included. An IL-10/IL-6 ratio greater than 1 had the highest sensitivity (89.39%, n = 278/311 eyes, n = 16 studies) for PVRL, where the sensitivity was not significantly different when only vitreous samples were drawn (88.89%, n = 232/261 eyes, n = 13 studies) compared to aqueous samples (83.33%, n = 20/24, n = 2) (p = 0.42). Flow cytometry of vitreous samples gave a positive result in 66/75 eyes (88.00%, n = 6 studies) with PVRL, and monoclonal IgH rearrangements on PCR gave a positive result in 354/416 eyes (85.10%, n = 20 studies) with PVRL. MYD88 L265P and CD79B mutation analysis performed poorly, yielding a positive result in 63/90 eyes (70.00%, n = 8 studies) with PVRL, and 20/57 eyes (35.09%, n = 4 studies) with PVRL, respectively. Overall, our systematic review found that an IL-10/IL-6 ratio greater or equal to one may provide the highest sensitivity in identifying patients with PVRL. Future studies are needed to employ multiple diagnostic tools to aid in the detection of PVRL and to further establish nuanced guidelines when determining the optimal diagnostic tool to use in diverse patient populations.
Topics: Humans; Retinal Neoplasms; Vitreous Body; Interleukin-10; Intraocular Lymphoma; Flow Cytometry; Interleukin-6; Myeloid Differentiation Factor 88; Diagnostic Techniques, Ophthalmological; Biomarkers, Tumor; CD79 Antigens; Polymerase Chain Reaction
PubMed: 38163550
DOI: 10.1016/j.survophthal.2023.12.001 -
The Cochrane Database of Systematic... Jan 2023Presbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual... (Review)
Review
BACKGROUND
Presbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual acuity and contrast sensitivity. One option of care for individuals with presbyopia and cataract is the use of multifocal or extended depth of focus intraocular lens (IOL) after cataract surgery. Although trifocal and bifocal IOLs are designed to restore three and two focal points respectively, trifocal lens may be preferable because it restores near, intermediate, and far vision, and may also provide a greater range of useful vision and allow for greater spectacle independence in individuals with presbyopia.
OBJECTIVES
To assess the effectiveness and safety of implantation with trifocal versus bifocal IOLs during cataract surgery among people with presbyopia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); Ovid MEDLINE; Embase.com; PubMed; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 31 March 2022. SELECTION CRITERIA: We included randomized controlled trials that compared trifocal and bifocal IOLs among participants 30 years of age or older with presbyopia undergoing cataract surgery.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence according to the GRADE classification.
MAIN RESULTS
We identified seven studies conducted in Europe and Turkey with a total of 331 participants. All included studies assessed visual acuity using a logarithm of the minimum angle of resolution (LogMAR chart). Of them, six (86%) studies assessed uncorrected distance visual acuity (the primary outcome of this review). Some studies also examined our secondary outcomes including uncorrected near, intermediate, and best-corrected distance visual acuity, as well as contrast sensitivity. Study characteristics All participants had bilateral cataracts with no pre-existing ocular pathologies or ocular surgery. Participants' mean age ranged from 55 to 74 years. Three studies reported on gender of participants, and they were mostly women. We assessed all of the included studies as being at unclear risk of bias for most domains. Two studies received financial support from manufacturers of lenses evaluated in this review, and at least one author of another study reported receiving payments for delivering lectures with lens manufacturers. Findings All studies compared trifocal versus bifocal IOL implantation on visual acuity outcomes measured on a LogMAR scale. At one year, trifocal IOL showed no evidence of effect on uncorrected distance visual acuity (mean difference (MD) 0.00, 95% confidence interval (CI) -0.04 to 0.04; I = 0%; 2 studies, 107 participants; low-certainty evidence) and uncorrected near visual acuity (MD 0.01, 95% CI -0.04 to 0.06; I = 0%; 2 studies, 107 participants; low-certainty evidence). Trifocal IOL implantation may improve uncorrected intermediate visual acuity at one year (MD -0.16, 95% CI -0.22 to -0.10; I = 0%; 2 studies, 107 participants; low-certainty evidence), but showed no evidence of effect on best-corrected distance visual acuity at one year (MD 0.00, 95% CI -0.03 to 0.04; I = 0%; 2 studies, 107 participants; low-certainty evidence). No study reported on contrast sensitivity or quality of life at one-year follow-up. Data from one study at three months suggest that contrast sensitivity did not differ between groups under photopic conditions, but may be worse in the trifocal group in one of the four frequencies under mesopic conditions (MD -0.19, 95% CI -0.33 to -0.05; 1 study; I = 0%, 25 participants; low-certainty evidence). One study examined vision-related quality of life using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at six months, and suggested no evidence of a difference between trifocal and bifocal IOLs (MD 1.41, 95% CI -1.78 to 4.60; 1 study, 40 participants; low-certainty evidence). Adverse events Adverse events reporting varied among studies. Of five studies reporting information on adverse events, two studies observed no intraoperative and postoperative complications or no posterior capsular opacification at six months. One study reported that glare and halos were similar to the preoperative measurements. One study reported that 4 (20%) and 10 (50%) participants had glare complaints at 6 months in trifocal and bifocal group, respectively (risk ratio 0.40, 95% CI 0.15 to 1.07; 40 participants). One study reported that four eyes (11.4%) in the bifocal group and three eyes (7.5%) in the trifocal group developed significant posterior capsular opacification requiring YAG capsulotomy at one year. The certainty of the evidence for adverse events was low.
AUTHORS' CONCLUSIONS
We found low-certainty of evidence that compared with bifocal IOL, implantation of trifocal IOL may improve uncorrected intermediate visual acuity at one year. However, there was no evidence of a difference between trifocal and bifocal IOL for uncorrected distance visual acuity, uncorrected near visual acuity, and best-corrected visual acuity at one year. Future research should include the comparison of both trifocal IOL and specific bifocal IOLs that correct intermediate visual acuity to evaluate important outcomes such as contrast sensitivity, quality of life, and vision-related adverse effects.
Topics: Aged; Female; Humans; Male; Middle Aged; Capsule Opacification; Cataract Extraction; Lenses, Intraocular; Presbyopia; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36705482
DOI: 10.1002/14651858.CD012648.pub3 -
Forensic Science, Medicine, and... Jun 2023The K and hypoxanthine (Hx) concentrations of the vitreous humour (VH) rise gradually after death, providing a means of estimating the post-mortem interval (PMI). The... (Review)
Review
The K and hypoxanthine (Hx) concentrations of the vitreous humour (VH) rise gradually after death, providing a means of estimating the post-mortem interval (PMI). The correlation between these analytes and the PMI is good since the vitreous chamber is partially isolated from autolytic events occurring elsewhere; the [K +] and [Hx] recorded is thus the result of changes within the eye. The present work provides a systematic review, following PRISMA recommendations, of 36 articles (3 reviews and 33 retrospective cohort studies) discussing the many procedures and regression models that have been developed for improving PMI estimates involving VH analytes. The results of a descriptive study are also provided, highlighting the causes and distribution of mortality as registered in medico-legal autopsies performed in 2019 in Galicia (northwestern Spain), and revealing the use of these PMI estimation methods in real forensic practice. Great heterogeneity was detected in the collection of VH samples, the treatments to which they were subjected before examination, and in their conservation and analysis. A lack of reproducibility in the analytical methods employed to estimate [K +] and [Hx] was noted, as well as an absence of external validation for most of the regression formulae used to determine the PMI from analyte values. The use of methods based on high-performance liquid chromatography, focal electrophoresis, or thermogravimetric/chemometric procedures might solve the problems encountered with traditional analytical techniques, offering reliable results more quickly and effectively (even when samples are contaminated). This study recommends using flexible multiple regression models that combine physical and chemical variables, and that population databases be constructed so that models can be properly validated.
Topics: Humans; Autopsy; Postmortem Changes; Vitreous Body; Spain; Reproducibility of Results; Retrospective Studies; Hypoxanthine
PubMed: 36271219
DOI: 10.1007/s12024-022-00539-5