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Experimental Eye Research Sep 2023Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies.... (Review)
Review
Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies. However, the current paucity of large animal models compared with rodent models constitutes a knowledge gap regarding the clinical translation of findings. Ocular anatomical and physiological similarities to humans suggest the pig as a relevant model animal. Thus, a systematic survey of porcine CNV models was performed to identify pertinent model parameters and suggest avenues for model standardization and optimization. A systematic search was performed in PubMed and EMBASE on November 28, 2022 for porcine models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. A total of 14 articles, representing 19 independent porcine CNV models were included. The included models were almost equally divided between laser-induced (53%) and surgically-induced (47%) models. Different specified breeds of domestic pigs (71%) were most commonly used in the studies. All studies used normal animals. Female pigs were reported used in 43% of the studies, while 43% did not report on sex of the animals. Younger pigs were typically used. The surgical models reported consistent CNV induction following mechanical Bruch's membrane rupture. The laser models used variants of the infrared diode laser (40%) or the frequency-doubled Nd:YAG laser (50%). Both lasers enabled successful CNV induction with reported induction rates ranging from 60 to 100%. Collateral damage to the neuroretina was reported for the infrared diode laser. CNV evaluation varied across studies with fluorescein angiography (50%) as the most used in vivo method and retinal sections (71%) as the most used ex vivo method. In interventional studies, quantification of lesions was in general performed between 7 and 14 days. The field of porcine CNV models is relatively small and heterogeneous and almost equally divided between surgically-induced and laser-induced models. Both methods have allowed successful modeling of CNV formation with induction rates comparable to those of non-human primates. However, the field would benefit from standardization of model parameters and reporting. This includes laser parameters and validation of CNV formation as well as methods of CNV evaluation and statistical analysis.
Topics: Female; Humans; Swine; Animals; Disease Models, Animal; Choroidal Neovascularization; Retina; Bruch Membrane; Fluorescein Angiography
PubMed: 37474015
DOI: 10.1016/j.exer.2023.109590 -
European Journal of Ophthalmology May 2024Age-related macular degeneration (AMD) is one of the leading causes of vision loss and blindness in older adults. Given the aging population in developed countries and... (Meta-Analysis)
Meta-Analysis Review
Age-related macular degeneration (AMD) is one of the leading causes of vision loss and blindness in older adults. Given the aging population in developed countries and the increased participation of older adults in the labour market, this paper aims to understand the impact of AMD on workplace productivity. Economic studies, comparative studies, observational studies, cohort studies, case series, randomized control trials, clinical trials, multicenter studies from MEDLINE, EMBASE, and CINHAL, as well as grey literature, were systematically searched to obtain all relevant literature. Duplicate records were removed, and two independent reviewers screened records for relevance. After screening, a risk of bias assessment was carried out. Data were extracted and a meta-analysis was performed using STATA 15.0. Fixed-effect and random-effect models were computed based on heterogeneity. Seven studies consisting of 3,060,864 subjects from 5 different countries were included in this systematic review. Mean wages lost due to impaired work productivity ranged from $1,395 to $55,180. The mean unemployment rate attributed to AMD ranged from 5.50% to 77.00%. Meta-analysis results indicated a significant unemployment rate (SMD = 0.44, CI: [0.27, 0.62]). Patients with AMD experience impaired work productivity as demonstrated by the wages lost and significantly higher rates of unemployment.
Topics: Humans; Macular Degeneration; Efficiency; Unemployment; Cost of Illness
PubMed: 37448315
DOI: 10.1177/11206721231185808 -
European Journal of Ophthalmology May 2024The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we... (Meta-Analysis)
Meta-Analysis Review
The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we screened all population-based studies that reported the prevalence of MMD, and pooled prevalence of MMD using a random-effect model. Subgroup analyses were performed to explore the differences in MMD prevalence in the general population and patients with high myopia according to ethnicity, region of residence (urban/rural), and grading system. Finally, 16 studies were included in this meta-analysis. Results obtained from 2,963 patients from seven countries on four continents indicated that the pooled prevalence of MMD in patients with high myopia was 49.0% (95% CI: 31.5%-66.7%). Results obtained from 71,052 participants from 10 countries on four continents suggested that the pooled prevalence of MMD in the general population was 1.7% (95% CI: 1.1%-2.6%). In the general population, living in urban areas and East Asians were associated with a high prevalence of MMD. Among patients with high myopia, only East Asians were at a higher risk of developing MMD. In conclusion, MMD was particularly prevalent in patients with high myopia. Compared with Europeans, East Asians (Chinese and Japanese) have a higher propensity of developing MMD, both in the general population and in patients with high myopia. It remains unclear whether the higher prevalence of MMD in patients with high myopia in East Asia is caused by differences in given age or given degree of myopia.Systematic review registration number: 202270014 (INPLASY.COM).
Topics: Humans; Prevalence; Myopia, Degenerative; Global Health; Macular Degeneration; Risk Factors
PubMed: 37439028
DOI: 10.1177/11206721231185816 -
Nutrients Apr 2023The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract,... (Review)
Review
The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.
Topics: Humans; Angiogenesis Inhibitors; Diet, Mediterranean; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Glaucoma; Cataract; Diabetic Retinopathy
PubMed: 37432187
DOI: 10.3390/nu15092043 -
Eye (London, England) Jan 2024TNF-α is a multifunctional cytokine produced by macrophages and T cells. This proinflammatory substance is considered to play a crucial role in the inflammatory process... (Review)
Review
TNF-α is a multifunctional cytokine produced by macrophages and T cells. This proinflammatory substance is considered to play a crucial role in the inflammatory process associated with age-related macular degeneration (AMD). The current review aimed to describe evidence for an association between TNF-α and AMD reported in various studies. The MEDLINE, Embase, PubMed and Global Health databases were systematically searched to identify studies that investigated the role of TNF-α in AMD. A total of 24 studies were deemed eligible for the review. To better understand and integrate the evidence, the studies were categorised into four major groups in relation to the role of TNF-α in AMD: (1) those examining biological signalling pathways through which TNF-α exerts its effect; (2) investigating levels of TNF-α; (3) exploring the genetics underlying the role of TNF-α; and (4) assessing anti-TNF-α agents as potential treatments for AMD. TNF-α is thought to directly contribute to choroidal neovascularization (CNV) enhancement and has been shown to exert its effect by augmenting the inflammatory response through other signalling pathways. Additionally, different genes have been found to be associated with activities linked to TNF-α in AMD. Overall, measurement of systemic and local levels of TNF-α has not yielded consistent findings, with variable conclusions for the role of anti-TNF-α agents in remission of AMD symptoms. The role of TNF-α in neovascular AMD is not clear, and not all anti-TNF-α agents are safe. The potential of this cytokine in atrophic AMD has not been examined. Future studies should address these unresolved questions.
Topics: Humans; Angiogenesis Inhibitors; Tumor Necrosis Factor-alpha; Cytokines; Tumor Necrosis Factor Inhibitors; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Choroidal Neovascularization
PubMed: 37380786
DOI: 10.1038/s41433-023-02634-5 -
The Cochrane Database of Systematic... Jun 2023Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques... (Review)
Review
BACKGROUND
Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond lasers can be used to perform the key steps in cataract surgery, such as corneal incisions, lens capsulotomy and fragmentation. The potential advantage of femtosecond laser-assisted cataract surgery (FLACS) is greater precision and reproducibility of these steps compared to manual techniques. The disadvantages are the costs associated with FLACS technology.
OBJECTIVES
To compare the effectiveness and safety of FLACS with standard ultrasound phacoemulsification cataract surgery (PCS) by gathering evidence from randomised controlled trials (RCTs).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov; the WHO ICTRP and the US Food and Drug Administration (FDA) website. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2022.
SELECTION CRITERIA
We included RCTs where FLACS was compared to PCS.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule, and posterior capsule tears. The secondary outcomes included corrected distance visual acuity (CDVA), quality of vision (as measured by any validated patient-reported outcome measure (PROM)), postoperative cystoid macular oedema complications, endothelial cell loss and cost-effectiveness. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 42 RCTs conducted in Europe, North America, South America and Asia, which enrolled a total of 7298 eyes of 5831 adult participants. Overall, the studies were at unclear or high risk of bias. In 16 studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Thirteen of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data. There was low-certainty evidence of little or no difference in the odds of developing anterior capsular tears when comparing FLACS and PCS (Peto odds ratio (OR) 0.83, 95% confidence interval (CI) 0.40 to 1.72; 5835 eyes, 27 studies) There was one fewer anterior capsule tear per 1000 operations in the FLACS group compared with the PCS group (95% CI 4 fewer to 3 more). There was low-certainty evidence of lower odds of developing posterior capsular tears with FLACS compared to PCS (Peto OR 0.50, 95% CI 0.25 to 1.00; 5767 eyes, 26 studies). There were four fewer posterior capsule tears per 1000 operations in the FLACS group compared with the PCS group (95% CI 6 fewer to same). There was moderate-certainty evidence of a very small advantage for the FLACS arm with regard to CDVA at six months or more follow-up, (mean difference (MD) -0.01 logMAR, 95% CI -0.02 to 0.00; 1323 eyes, 7 studies). This difference is equivalent to 1 logMAR letter between groups and is not thought to be clinically important. From the three studies (1205 participants) reporting a variety of PROMs (Cat-PROMS, EQ-5D, EQ-SD-3L, Catquest9-SF and patient survey) up to three months following surgery, there was moderate-certainty evidence of little or no difference in the various parameters between the two treatment arms. There was low-certainty evidence of little or no difference in the odds of developing cystoid macular oedema when comparing FLACS and PCS (Peto OR 0.84, 95% CI 0.56 to 1.28; 4441 eyes, 18 studies). There were three fewer cystoid macular oedema cases per 1000 operations in the FLACS group compared with the PCS group (95% CI 10 fewer to 6 more). In one study the incremental cost-effectiveness ratio (ICER) (cost difference divided by quality-adjusted life year (QALY) difference) was GBP £167,620 when comparing FLACS to PCS. In another study, the ICER was EUR €10,703 saved per additional patient who had treatment success with PCS compared to FLACS. Duration ranged from three minutes in favour of FLACS to eight minutes in favour of PCS (I = 100%, 11 studies) (low-certainty evidence). There was low-certainty evidence of little or no important difference in endothelial cell loss when comparing FLACS with PCS (MD 12 cells per mm in favour of FLACS, 95% CI -40 to 64; 1512 eyes, 10 studies). AUTHORS' CONCLUSIONS: This review of 42 studies provides evidence that there is probably little or no difference between FLACS and PCS in terms of intraoperative and postoperative complications, postoperative visual acuity and quality of life. Evidence from two studies suggests that FLACS may be the less cost-effective option. Many of the included studies only investigated very specific outcome measures such as effective phacoemulsification time, endothelial cell count change or aqueous flare, rather than those directly related to patient outcomes. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis, and guidance on this has been recently published.
Topics: Humans; Phacoemulsification; Macular Edema; Cataract Extraction; Cataract; Lasers
PubMed: 37369549
DOI: 10.1002/14651858.CD010735.pub3 -
Acta Ophthalmologica May 2024The aim of the study was to determine the efficacy and safety of combined anti-VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Anti-VEGF and steroid combination therapy relative to anti-VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta-analysis of safety.
The aim of the study was to determine the efficacy and safety of combined anti-VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta-analysis of peer-reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti-VEGF/steroids versus anti-VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti-VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti-VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP-related adverse events (RR = 0.10, 95% CI = [0.02, 0.42], p = 0.002) and cataract-related adverse events (RR = 0.10, 95% CI = [0.01, 0.71], p = 0.02). Our systematic review and meta-analysis of seven studies and 452 eyes revealed that combination therapy of anti-VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short-term visual outcomes in two studies, while others reported no difference between treatment groups. Meta-analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub-optimal response to anti-VEGF treatment.
Topics: Humans; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Steroids; Vascular Endothelial Growth Factor A
PubMed: 37365698
DOI: 10.1111/aos.15724 -
Avicenna Journal of Phytomedicine 2023Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option... (Review)
Review
OBJECTIVE
Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option with minimal side effects for the treatment of retinopathy by reducing the symptoms and improving visual acuity. The purpose of this systematic review was to collect studies on the effectiveness of medicinal plants in the treatment or prevention of retinopathy.
MATERIALS AND METHODS
A systematic literature search was performed in PubMed, Scopus, Google Scholar, and other databases in April 2021 using "herbal products" and "Retinopathy" with all their equivalent and similar terms. For this purpose, human clinical trials with the English language were included and articles with subject irrelevancy were excluded from further evaluation.
RESULTS
Overall, 30 articles with 2324 patients were studied for possible effects of herbal therapy on retinopathy. From 30 included articles, different herbal products had been evaluated. Out of 30 selected articles, 11 articles were for the treatment of age-related macular degeneration (AMD), 14 articles covered patients with diabetic retinopathy, and the other five studies were for other retinal disorders. The outcomes in majority of the studies include changes in visual acuity (VA), fundus performance, best-corrected visual acuity (BCVA), central macular thickness (CMT), focal electroretinogram (fERG), supplements and adjuvant medications appeared to be more beneficial in patients with AMD and diabetic maculopathy.
CONCLUSION
Herbal therapy can be considered as a potential candidate in the adjuvant and complementary therapies of retinopathy. However, further studies are required to verify such efficiency.
PubMed: 37333471
DOI: 10.22038/AJP.2022.62423.2977 -
Frontiers in Medicine 2023Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective...
Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective of this review is to assess the most recent research on the ideal dietary approach to prevent or support the treatment of DR, AMD, and cataracts, as well as to construct a food pyramid that makes it simple for people who are at risk of developing these pathologies to decide what to eat. The food pyramid presented here proposes what should be consumed every day: 3 portions of low glycemic index (GI) grains (for fiber and zinc content), 5 portions (each portion: ≥200 g/day) of fruits and vegetables (spinach, broccoli, zucchini cooked, green leafy vegetables, orange, kiwi, grapefruit for folic acid, vitamin C, and lutein/zeaxanthin content, at least ≥42 μg/day, are to be preferred), extra virgin olive (EVO) oil (almost 20 mg/day for vitamin E and polyphenols content), nuts or oil seeds (20-30 g/day, for zinc content, at least ≥15.8 mg/day); weekly: fish (4 portions, for omega-3 content and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) 0.35-1.4 g/day), white meat (3 portions for vitamin B12 content), legumes (2 portions for vegetal proteins), eggs (2 portions for lutein/zeaxanthin content), light cheeses (2 portions for vitamin B6 content), and almost 3-4 times/week microgreen and spices (saffron and curcumin). At the top of the pyramid, there are two pennants: one green, which indicates the need for personalized supplementation (if daily requirements cannot be met through diet, omega-3, and L-methylfolate supplementation), and one red, which indicates that certain foods are prohibited (salt and sugar). Finally, 3-4 times per week, 30-40 min of aerobic and resistance exercises are required.
PubMed: 37324128
DOI: 10.3389/fmed.2023.1168560 -
The Cochrane Database of Systematic... Jun 2023Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as populations age, AMD remains incurable and there are no treatments for most patients. Mounting genetic and molecular evidence implicates complement system overactivity as a key driver of AMD development and progression. The last decade has seen the development of several novel therapeutics targeting complement in the eye for the treatment of AMD. This review update encompasses the results of the first randomised controlled trials in this field.
OBJECTIVES
To assess the effects and safety of complement inhibitors in the prevention or treatment of AMD.
SEARCH METHODS
We searched CENTRAL on the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP to 29 June 2022 with no language restrictions. We also contacted companies running clinical trials for unpublished data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with parallel groups and comparator arms that studied complement inhibition for advanced AMD prevention/treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed search results and resolved discrepancies through discussion. Outcome measures evaluated at one year included change in best-corrected visual acuity (BCVA), untransformed and square root-transformed geographic atrophy (GA) lesion size progression, development of macular neovascularisation (MNV) or exudative AMD, development of endophthalmitis, loss of ≥ 15 letters of BCVA, change in low luminance visual acuity, and change in quality of life. We assessed risk of bias and evidence certainty using Cochrane risk of bias and GRADE tools.
MAIN RESULTS
Ten RCTs with 4052 participants and eyes with GA were included. Nine evaluated intravitreal (IVT) administrations against sham, and one investigated an intravenous agent against placebo. Seven studies excluded patients with prior MNV in the non-study eye, whereas the three pegcetacoplan studies did not. The risk of bias in the included studies was low overall. We also synthesised results of two intravitreal agents (lampalizumab, pegcetacoplan) at monthly and every-other-month (EOM) dosing intervals. Efficacy and safety of IVT lampalizumab versus sham for GA For 1932 participants in three studies, lampalizumab did not meaningfully change BCVA given monthly (+1.03 letters, 95% confidence interval (CI) -0.19 to 2.25) or EOM (+0.22 letters, 95% CI -1.00 to 1.44) (high-certainty evidence). For 1920 participants, lampalizumab did not meaningfully change GA lesion growth given monthly (+0.07 mm², 95% CI -0.09 to 0.23; moderate-certainty due to imprecision) or EOM (+0.07 mm², 95% CI -0.05 to 0.19; high-certainty). For 2000 participants, lampalizumab may have also increased MNV risk given monthly (RR 1.77, 95% CI 0.73 to 4.30) and EOM (RR 1.70, 95% CI 0.67 to 4.28), based on low-certainty evidence. The incidence of endophthalmitis in patients treated with monthly and EOM lampalizumab was 4 per 1000 (0 to 87) and 3 per 1000 (0 to 62), respectively, based on moderate-certainty evidence. Efficacy and safety of IVT pegcetacoplan versus sham for GA For 242 participants in one study, pegcetacoplan probably did not meaningfully change BCVA given monthly (+1.05 letters, 95% CI -2.71 to 4.81) or EOM (-1.42 letters, 95% CI -5.25 to 2.41), as supported by moderate-certainty evidence. In contrast, for 1208 participants across three studies, pegcetacoplan meaningfully reduced GA lesion growth when given monthly (-0.38 mm², 95% CI -0.57 to -0.19) and EOM (-0.29 mm², 95% CI -0.44 to -0.13), with high certainty. These reductions correspond to 19.2% and 14.8% versus sham, respectively. A post hoc analysis showed possibly greater benefits in 446 participants with extrafoveal GA given monthly (-0.67 mm², 95% CI -0.98 to -0.36) and EOM (-0.60 mm², 95% CI -0.91 to -0.30), representing 26.1% and 23.3% reductions, respectively. However, we did not have data on subfoveal GA growth to undertake a formal subgroup analysis. In 1502 participants, there is low-certainty evidence that pegcetacoplan may have increased MNV risk when given monthly (RR 4.47, 95% CI 0.41 to 48.98) or EOM (RR 2.29, 95% CI 0.46 to 11.35). The incidence of endophthalmitis in patients treated with monthly and EOM pegcetacoplan was 6 per 1000 (1 to 53) and 8 per 1000 (1 to 70) respectively, based on moderate-certainty evidence. Efficacy and safety of IVT avacincaptad pegol versus sham for GA In a study of 260 participants with extrafoveal or juxtafoveal GA, monthly avacincaptad pegol probably did not result in a clinically meaningful change in BCVA at 2 mg (+1.39 letters, 95% CI -5.89 to 8.67) or 4 mg (-0.28 letters, 95% CI -8.74 to 8.18), based on moderate-certainty evidence. Despite this, the drug was still found to have probably reduced GA lesion growth, with estimates of 30.5% reduction at 2 mg (-0.70 mm², 95% CI -1.99 to 0.59) and 25.6% reduction at 4 mg (-0.71 mm², 95% CI -1.92 to 0.51), based on moderate-certainty evidence. Avacincaptad pegol may have also increased the risk of developing MNV (RR 3.13, 95% CI 0.93 to 10.55), although this evidence is of low certainty. There were no cases of endophthalmitis reported in this study.
AUTHORS' CONCLUSIONS
Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.
Topics: Humans; Administration, Intravenous; Complement Inactivating Agents; Endophthalmitis; Geographic Atrophy; Macular Degeneration
PubMed: 37314061
DOI: 10.1002/14651858.CD009300.pub3