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Medicine Nov 2022Cataracts and age-related macular degeneration (AMD) are common causes of decreased vision and blindness in individuals over age 50. Although surgery is the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cataracts and age-related macular degeneration (AMD) are common causes of decreased vision and blindness in individuals over age 50. Although surgery is the most effective treatment for cataracts, it may accelerate the progression of AMD, so this study further evaluated the influence of cataract surgery for AMD through a systematic review and meta-analysis.
METHODS
The Cochrane Systematic Evaluation method was adopted, and computer searches were conducted for the China Knowledge Network, Wanfang, Vipul, SinoMed, PubMed, SpringerLink, Clinicalkey, Medline, Cochrane Library, Web of Science, OVID, and Embase databases of cohort studies on the impact of cataract surgery on AMD, with search timeframes up to May 2022. Meta-analysis was performed using Stata/12.0.
RESULTS
A total of 8 cohort studies were included in the study. The results showed that the relative risk (RR) of AMD progression after cataract surgery was not significantly different, RR 1.194 [95% credibility interval (CI) 0.897-1.591]; the risk remained increased more than 5 years after surgery, RR 1.372 (95% CI 1.062-1.772).
CONCLUSION
There is still a significant positive correlation between cataract surgery and increase the risk of worsening of AMD progression, and faster progression of early-to-late AMD found in cataract surgery with longer follow-up of patients.
Topics: Humans; Middle Aged; Cataract Extraction; Macular Degeneration; Cataract; China
PubMed: 36343088
DOI: 10.1097/MD.0000000000031566 -
The Cochrane Database of Systematic... Oct 2022Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU.
OBJECTIVES
To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group.
AUTHORS' CONCLUSIONS
There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.
Topics: Adult; Humans; Macular Edema; Cyclosporine; Mycophenolic Acid; Tacrolimus; Azathioprine; Methotrexate; Steroids; Immunosuppressive Agents; Panuveitis; Inflammation; Antirheumatic Agents
PubMed: 36315029
DOI: 10.1002/14651858.CD014831.pub2 -
Nutrients Oct 2022: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if... (Meta-Analysis)
Meta-Analysis Review
: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus -3 long-chain polyunsaturated fatty acids (-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA) (SMD: -1.99, 95% CI: -3.33, -0.65) compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall (SMD: 4.59, 95% CI: 1.75, 7.43) after lutein plus zeaxanthin supplementation. Combinations of lutein and zeaxanthin with -3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of -3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients.
Topics: Humans; Zeaxanthins; Lutein; Xanthophylls; Visual Acuity; Double-Blind Method; Macular Degeneration; Dietary Supplements; Fatty Acids, Omega-3
PubMed: 36296956
DOI: 10.3390/nu14204273 -
Advances in Therapy Dec 2022We investigated effectiveness and safety outcomes of diabetic macula edema (DME) treatment in routine clinical practice. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
We investigated effectiveness and safety outcomes of diabetic macula edema (DME) treatment in routine clinical practice.
METHODS
A literature search was conducted of peer-reviewed articles published from January 2011 to September 2021. Studies of DME treatment in real-world practice of at least 6 months with at least 50 eyes at baseline were included. Randomized controlled trials (RCTs) were excluded. The primary outcome for this meta-analysis was change in visual acuity (VA) 12 months after starting treatment.
RESULTS
Of 3034 initially identified studies, 138 met selection criteria, representing more than 40,000 eyes. The mean 12-month VA gain was 4.6 letters (95% CI 3.7, 5.4; baseline 58.6) for vascular endothelial growth factor inhibitors (anti-VEGF), 4.4 (2.5, 6.3; baseline 54.2) for steroids, and 2.1 (- 1.2, 5.3; baseline 63.6) for macular laser. Australian and New Zealand studies had better baseline VA when initiating treatment compared with Asia, Europe, and North America, translating to better VA at 12 months. Fewer anti-VEGF injections were delivered in real-world practice than registrational RCTs. Neither systemic nor ocular safety was consistently reported.
CONCLUSIONS
Intravitreal anti-VEGF or steroids for DME generally led to visual gains in real-world practice but these were less impressive than RCTs, with undertreatment and differences in baseline characteristics likely contributing factors.
Topics: Humans; Ranibizumab; Bevacizumab; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A; Australia; Macular Edema; Diabetic Retinopathy; Angiogenesis Inhibitors; Antibodies, Monoclonal; Steroids; Edema; Intravitreal Injections; Diabetes Mellitus
PubMed: 36241963
DOI: 10.1007/s12325-022-02326-8 -
European Journal of Ophthalmology Oct 2022There is an increasing shift towards non-communicable eye diseases (NCEDs) because of a demographic transition. Incorporation of telemedicine into everyday clinical...
BACKGROUND
There is an increasing shift towards non-communicable eye diseases (NCEDs) because of a demographic transition. Incorporation of telemedicine into everyday clinical practice is becoming increasingly popular. We sought to carry out a systematic review to look at which applications on portable devices are available for use in eyecare practices for patients with NCEDs, specifically refractive error, diabetic retinopathy, age-related macular degeneration (AMD) and glaucoma.
METHODS
Pubmed, EMBASE, Medline, PsychInfo databases were systematically searched using keywords and MeSH terms. Eligible articles included peer-reviewed, original full text articles evaluating apps for use on portable devices aimed at patients with NCEDs.
RESULTS
The initial search yielded 100 studies. Nine studies met the inclusion criteria, and an additional eight studies were identified through reference screening. Of the included studies, 29.4%% (n = 5) evaluated applications aimed for use to identify refractive errors, 35.3% (n = 6) aimed at patients with glaucoma, 23.5% (n = 4) for use by patients with AMD, 11.7% (n = 2) for the non-specific monitoring of visual acuity/fields. 76.5% (n = 13) of the studies showed that the application evaluated was an effective and reliable tool compared to clinical standards.
CONCLUSIONS
Portable device applications in patients with NCED have been shown to be effective. The use of these apps for patients is limited to either diagnostic or monitoring use. There is scope for apps which encompass other aspects of patient care that have been used in other specialties that may be applied to ophthalmic patients, including those with an educational aim which have a role in increasing compliance.
PubMed: 36199266
DOI: 10.1177/11206721221131397 -
International Journal of Retina and... Sep 2022Aflibercept is a relatively new anti-VEGF used to treat neovascular age-related macular degeneration (AMD). The purpose of this review is to evaluate the effect of pro... (Review)
Review
BACKGROUND
Aflibercept is a relatively new anti-VEGF used to treat neovascular age-related macular degeneration (AMD). The purpose of this review is to evaluate the effect of pro re nata (PRN) and fixed regimen (bimonthly) of aflibercept injection for neovascular AMD on visual outcomes at 12 months of follow-up.
METHODS
We conducted a systematic search in PubMed (MEDLINE), Embase, Scopus, and Web of Science, EBSCOHost, and ClinicalTrials.gov databases. Number of injections, number of hospital visit, mean change of best corrected visual acuity (BCVA), mean change of central macular thickness (CMT), and adverse effects of the included studies were evaluated. Meta-analysis were performed using Review Manager 5.4.
RESULTS
Four studies were selected for meta-analyses synthesis (3 RCT, 1 retrospective study). A total of 197 eyes in PRN group and 241 eyes in the fixed group. All four studies favored fixed regimen with standardized mean difference of 0.56 (95% CI 0.36-0.75, I = 0%, p < 0.00001). There was no significant difference in CMT between both group with SMD of 0.17 (95% CI - 0.14-0.48, I = 26%, p = 0.28).
CONCLUSION
The present meta-analysis shows that bimonthly injection of aflibercept for neovascular AMD is superior compared to PRN injection, shown by better improvement in BCVA at 12 months follow-up. However, high risk of bias downgrade the certainty of evidence.
PubMed: 36138445
DOI: 10.1186/s40942-022-00416-x -
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 -
Acta Ophthalmologica Mar 2023Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD).... (Review)
Review
Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 μm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 μm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Intravitreal Injections; Macular Degeneration; Receptors, Vascular Endothelial Growth Factor; Diabetic Retinopathy; Recombinant Fusion Proteins; Wet Macular Degeneration
PubMed: 36117281
DOI: 10.1111/aos.15242 -
BMJ Open Ophthalmology Jun 2022This systematic review assessed the long-term outcomes for patients treated with intravitreal antivascular endothelial growth factor or dexamethasone for macular oedema... (Review)
Review
This systematic review assessed the long-term outcomes for patients treated with intravitreal antivascular endothelial growth factor or dexamethasone for macular oedema (MO) secondary to retinal vein occlusion (RVO). Studies investigating patients of all ages with MO due to RVO only were included. The review was deliberately broad in scope, including comparative and non-comparative studies to ensure inclusion of real-world type evidence. Risk of bias was assessed. In total, 76 data sets were included (10 775 participants). Overall, mean best-corrected visual acuity (BCVA) improved from baseline to 5 years by 16.1 letters (p<0.01). BCVA improved from baseline in both central RVO (CRVO) and branch RVO (BRVOs) at 2 years, by 9.1 (p<0.01) (difference from baseline in CRVOs) and 9.1 (p<0.01) letters, respectively. At 5 years, BCVA improved from baseline in CRVOs by 15.6 letters and in BRVOs by 16.2; the difference between RVO types was not significant (p=0.18). Two studies had 5-year data for ranibizumab, and improvement was evident. There was no significant difference between outcomes in randomised controlled trials (RCTs) compared with non RCTs. These results suggest a benefit to receiving long-term intravitreal treatments for MO due to RVO.
Topics: Glucocorticoids; Humans; Macular Edema; Ranibizumab; Retinal Vein Occlusion; Visual Acuity
PubMed: 36063388
DOI: 10.1136/bmjophth-2022-001010 -
Journal of Clinical Medicine Aug 2022The purpose of this study was to provide an estimate of the number of current and future patients with polypoidal choroidal vasculopathy (PCV) in Europe. We... (Review)
Review
The purpose of this study was to provide an estimate of the number of current and future patients with polypoidal choroidal vasculopathy (PCV) in Europe. We systematically searched 11 literature databases on 18 May 2022 for studies on the prevalence of PCV among a consecutive and representative group of patients with suspected neovascular age-related macular degeneration (AMD). Prevalence of PCV in patients with suspected neovascular AMD was summarized and included in a prevalence meta-analysis. We then used current population data and population forecasts by Eurostat and the Office for National Statistics to determine current and future number of patients with neovascular AMD in Europe. Then, we calculated the number of patients with PCV with our calculated estimate of the prevalence of PCV among Europeans suspected with neovascular AMD. A total of five eligible studies were identified which included a total of 1359 patients. All these studies used the gold standard of indocyanine green angiography as a routine part of their diagnostic approach. Among patients undergoing detailed retinal examination for suspected neovascular AMD, our meta-analysis calculated the prevalence of PCV to be 8.3% (95% confidence interval: 6.8-9.8%). Our population estimates find that a total of 217,404 patients with PCV exist in Europe in the year 2022, which constitutes 0.04% of the entire population of Europe. This number is estimated to increase to 287,517 patients in the year 2040. Our estimates are important for different healthcare stakeholders, especially when planning and allocating expensive resources.
PubMed: 36013005
DOI: 10.3390/jcm11164766