-
Survey of Ophthalmology 2024With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to... (Meta-Analysis)
Meta-Analysis
With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence.
Topics: Humans; Complement C3; Complement C5; Complement Inactivating Agents; Geographic Atrophy; Macular Degeneration; Visual Acuity
PubMed: 38008405
DOI: 10.1016/j.survophthal.2023.11.008 -
Survey of Ophthalmology 2023There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal... (Meta-Analysis)
Meta-Analysis Review
There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Polypoidal Choroidal Vasculopathy; Bevacizumab; Intravitreal Injections; Observational Studies as Topic
PubMed: 37146693
DOI: 10.1016/j.survophthal.2023.04.002 -
Journal of Global Health 2022Myopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for...
BACKGROUND
Myopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization.
METHODS
A systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict.
RESULTS
After applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty.
CONCLUSIONS
The outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.
Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Humans; Macular Degeneration; Myopia, Degenerative; Ranibizumab
PubMed: 35356661
DOI: 10.7189/jogh.12.04026 -
Retina (Philadelphia, Pa.) Nov 2022This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular... (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration.
METHODS
A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model.
RESULTS
Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points.
CONCLUSION
There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.
Topics: Humans; Bevacizumab; Endothelial Growth Factors; Intravitreal Injections; Macular Degeneration; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Uveitis
PubMed: 36269802
DOI: 10.1097/IAE.0000000000003582 -
Journal of Ophthalmology 2022Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive... (Review)
Review
OBJECTIVES
Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities.
METHODS
The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies.
RESULTS
A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative variants to wild type or exon-skipping therapy for -linked AS with truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease.
CONCLUSIONS
The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.
PubMed: 36119140
DOI: 10.1155/2022/9250367 -
Molecular Diagnosis & Therapy Nov 2021The purpose of the review was to identify structural, functional, blood-based, and other types of biomarkers for early, intermediate, and late nonexudative stages of...
TOPIC
The purpose of the review was to identify structural, functional, blood-based, and other types of biomarkers for early, intermediate, and late nonexudative stages of age-related macular degeneration (AMD) and summarize the relevant data for proof-of-concept clinical trials.
CLINICAL RELEVANCE
AMD is a leading cause of blindness in the aging population, yet no treatments exist for its most common nonexudative form. There are limited data on the diagnosis and progression of nonexudative AMD compared to neovascular AMD. Our objective was to provide a comprehensive, systematic review of recently published biomarkers (molecular, structural, and functional) for early AMD, intermediate AMD, and geographic atrophy and to evaluate the relevance of these biomarkers for use in future clinical trials.
METHODS
A literature search of PubMed, ScienceDirect, EMBASE, and Web of Science from January 1, 1996 to November 30, 2020 and a patent search were conducted. Search terms included "early AMD," "dry AMD," "intermediate AMD," "biomarkers for nonexudative AMD," "fundus autofluorescence patterns," "color fundus photography," "dark adaptation," and "microperimetry." Articles were assessed for bias and quality with the Mixed-Methods Appraisal Tool. A total of 94 articles were included (61,842 individuals).
RESULTS
Spectral-domain optical coherence tomography was superior at highlighting detailed structural changes in earlier stages of AMD. Fundus autofluorescence patterns were found to be most important in estimating progression of geographic atrophy. Delayed rod intercept time on dark adaptation was the most widely recommended surrogate functional endpoint for early AMD, while retinal sensitivity on microperimetry was most relevant for intermediate AMD. Combinational studies accounting for various patient characteristics and machine/deep-learning approaches were best suited for assessing individualized risk of AMD onset and progression.
CONCLUSION
This systematic review supports the use of structural and functional biomarkers in early AMD and intermediate AMD, which are more reproducible and less invasive than the other classes of biomarkers described. The use of deep learning and combinational algorithms will gain increasing importance in future clinical trials of nonexudative AMD.
Topics: Aged; Angiogenesis Inhibitors; Biomarkers; Geographic Atrophy; Humans; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 34432254
DOI: 10.1007/s40291-021-00551-5 -
Survey of Ophthalmology 2023Optical coherence tomography is a noninvasive imaging technology using the optical reflectivity of tissues that is capable of detecting quantitative and qualitative... (Meta-Analysis)
Meta-Analysis Review
Optical coherence tomography is a noninvasive imaging technology using the optical reflectivity of tissues that is capable of detecting quantitative and qualitative biomarkers of age-related macular degeneration (AMD) that cannot be similarly recognized in conventional imaging. We systematically searched PubMed and Embase databases to identify relevant articles to this subject. A fixed-effect or random-effect model was applied for the meta-analysis based on the heterogeneity level. In addition, subgroup analyses, meta-regression, publication bias, and quality assessment were also performed. Twenty-five studies with 1,632 cases and 1,445 healthy controls in total were included. Our results revealed that, when compared to controls, AMD subjects showed a significantly lower thickness in the choroid at 500 µm temporal, 1,500 µm nasal, and temporal to the fovea, subfoveal choroid, average peripapillary retinal nerve fiber layer, and average macular ganglion cell complex (GCC); however, average and central choroidal thickness 500 µm nasal, 1,000 µm nasal and temporal to the fovea, central and parafoveal macular GCC, retinal nerve fiber layer, and inner plexiform layer, and central macular thickness did not change significantly. Various regional analyses showed several other significant differences. The findings of the current study confirm that some retinal layers are altered in AMD patients compared to healthy controls. Thus, future studies are required to derive more definitive conclusions.
Topics: Humans; Tomography, Optical Coherence; Nerve Fibers; Retinal Ganglion Cells; Choroid; Macular Degeneration
PubMed: 35908660
DOI: 10.1016/j.survophthal.2022.07.006 -
Clinical Ophthalmology (Auckland, N.Z.) 2022This systematic review explores the use of artificial intelligence (AI) in the analysis of biofluid markers in age-related macular degeneration (AMD). We detail the... (Review)
Review
This systematic review explores the use of artificial intelligence (AI) in the analysis of biofluid markers in age-related macular degeneration (AMD). We detail the accuracy and validity of AI in diagnostic and prognostic models and biofluid markers that provide insight into AMD pathogenesis and progression. This review was conducted in accordance with the Preferred Reporting Items for a Systematic Review and Meta-analysis guidelines. A comprehensive search was conducted across 5 electronic databases including Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EMBASE, Medline, and Web of Science from inception to July 14, 2021. Studies pertaining to biofluid marker analysis using AI or bioinformatics in AMD were included. Identified studies were assessed for risk of bias and critically appraised using the Joanna Briggs Institute Critical Appraisal tools. A total of 10,264 articles were retrieved from all databases and 37 studies met the inclusion criteria, including 15 cross-sectional studies, 15 prospective cohort studies, five retrospective cohort studies, one randomized controlled trial, and one case-control study. The majority of studies had a general focus on AMD (58%), while neovascular AMD (nAMD) was the focus in 11 studies (30%), and geographic atrophy (GA) was highlighted by three studies. Fifteen studies examined disease characteristics, 15 studied risk factors, and seven guided treatment decisions. Altered lipid metabolism (HDL-cholesterol, total serum triglycerides), inflammation (c-reactive protein), oxidative stress, and protein digestion were implicated in AMD development and progression. AI tools were able to both accurately differentiate controls and AMD patients with accuracies as high as 87% and predict responsiveness to anti-VEGF therapy in nAMD patients. Use of AI models such as discriminant analysis could inform prognostic and diagnostic decision-making in a clinical setting. The identified pathways provide opportunity for future studies of AMD development and could be valuable in the advancement of novel treatments.
PubMed: 35968055
DOI: 10.2147/OPTH.S377262 -
The Cochrane Database of Systematic... May 2021Age-related macular degeneration (AMD) is one of the leading causes of blindness in high-income countries. The majority of cases of AMD are of the non-exudative type.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is one of the leading causes of blindness in high-income countries. The majority of cases of AMD are of the non-exudative type. Experts have proposed photobiomodulation (PBM) therapy as a non-invasive procedure to restore mitochondrial function, upregulate cytoprotective factors and prevent apoptotic cell death in retinal tissue affected by AMD.
OBJECTIVES
To assess the effectiveness and safety of PBM compared to standard care, no treatment or sham treatment for people with non-exudative AMD.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 5, 2020), Ovid MEDLINE, Embase, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to 11 May 2020 with no language restrictions.
SELECTION CRITERIA
The review included randomised controlled trials (RCTs) on participants receiving any type of PBM therapy for non-exudative AMD compared to standard care, sham treatment or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We considered the following outcome measures at 12 months: best-corrected visual acuity (BCVA) ; contrast sensitivity; near vision; low luminance density score; reading speed; vision-related quality of life score; and adverse events such as progression of AMD and conversion to exudative AMD. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included two published RCTs from single centres in the UK and Canada, which recruited 60 participants (60 eyes) and 30 participants (46 eyes) respectively. Participants in these trials were people with non-exudative AMD with Age-Related Eye Disease Study (AREDS) categories 2 to 4. One study compared single wavelength PBM with no treatment. This study was at risk of performance bias because the study was not masked, and there was attrition bias. One study compared multi-wavelength PBM with sham treatment and conflicts of interest were reported by study investigators. We also identified three eligible ongoing RCTs from searching the clinical trials database. When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in BCVA at 12 months (mean difference (MD) 0.02 logMAR, 95% confidence interval (CI) -0.02 to 0.05; 2 RCTs, 90 eyes; low-certainty evidence). One study comparing multi-wavelength PBM with sham treatment showed an improvement in contrast sensitivity at Level E (18 cycles/degree) at 12 months (MD 0.29 LogCS, 95% CI 0.23 to 0.35; 1 RCT, 46 eyes; low-certainty evidence). Visual function and health-related quality of life scores were comparable between single wavelength PBM and no treatment groups at 12 months (VFQ-48 score MD 0.43, 95% CI -0.17 to 1.03; P = 0.16; 1 RCT, 47 eyes; low-certainty evidence). When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in conversion to exudative AMD (risk ratio (RR) 0.97, 95% CI 0.17 to 5.44; 2 RCTs, 96 eyes; very low-certainty evidence) at 12 months. There was inconclusive evidence that single wavelength PBM prevents the progression of AMD (RR 0.79, 95% CI 0.41 to 1.53; P = 0.48; 1 RCT, 50 eyes; low-certainty evidence). Disease progression was defined as the development of advanced AMD or significant increase in drusen volume. No included study reported near vision, low luminance vision or reading speed outcomes.
AUTHORS' CONCLUSIONS
Currently there remains uncertainty whether PBM treatment is beneficial in slowing progression of non-exudative macular degeneration. There is a need for further well-designed controlled trials assessing dosimetry, powered for both effectiveness and safety outcomes. Consideration should be given to the adoption of agreed clinical outcome measures and patient-based outcome measures for AMD.
Topics: Bias; Confidence Intervals; Contrast Sensitivity; Disease Progression; Humans; Low-Level Light Therapy; Macular Degeneration; Outcome Assessment, Health Care; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Visual Acuity
PubMed: 34097768
DOI: 10.1002/14651858.CD013029.pub2 -
Eye (London, England) Jan 2023This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related... (Meta-Analysis)
Meta-Analysis Review
This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections.
Topics: Humans; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Clinical Protocols; Intravitreal Injections; Treatment Outcome; Recombinant Fusion Proteins; Wet Macular Degeneration; Randomized Controlled Trials as Topic
PubMed: 35396574
DOI: 10.1038/s41433-022-02020-7