Potential role of lampalizumab for treatment of&amp;nbsp;geographic atrophy

Rhoades, William; Dickson, Drew; Diana, V.

doi:10.2147/opth.s59725

Cited by 14 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observations may have important implications in future management of nAMD. Complement inhibitors are currently in clinical trials for AMD [ 23 , 24 ], and the identification of suitable patients is important for the success of this type of immune therapy. Our results provide evidence that nAMD patients with CNV and with subretinal fibrosis may benefit more from the complement inhibitor therapy compared to other subgroups of nAMD patients.…”

Section: Discussionmentioning

confidence: 99%

“…It is clear that uncontrolled or dysregulated complement activation may contribute to macular lesion development in AMD, which offers the opportunities for complement-targeted immune therapy. Indeed a number of complement inhibitors are in phase I, II and III clinical trials for AMD [ 23 , 24 ]. In view of the diversity of AMD phenotype, it is likely that different immune mechanisms may be involved in different types of AMD, and this is exemplified by the diverse response to anti-VEGF therapy observed in various clinical studies [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

et al. 2016

View full text Add to dashboard Cite

BackgroundThe aim of this study was to investigate the plasma levels of complement C3a, C4a, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy.ResultsNinety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case–control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4a and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4a and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4a and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy.ConclusionsOur results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-016-0060-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

et al. 2016

View full text Add to dashboard Cite

show abstract

“… 99 The 18-month Phase II MAHALO study assessed the efficacy of monthly intravitreal injections of lampalizumab in halting the progression of GA in patients with bilateral disease. 100 Lampalizumab (anti-factor D Fab) is a humanized monoclonal antibody (Fab fragment), which is a selective inhibitor of complement factor D ( CFD ). Using autofluorescence and color fundus photographs, it was found that patients had a 20% reduction in mean change from baseline in the GA area at month 18.…”

Section: Prophylaxis and Treatment Of Dry Amdmentioning

confidence: 99%

Recent developments in age-related macular degeneration: a review

Al-Zamil¹,

Yassin²

2017

CIA

346

251

View full text Add to dashboard Cite

Background: Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective: The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods: An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results: Several risk factors have been linked to AMD, such as age (.60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion: Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome.

show abstract

“…Currently, potential candidates, such as complement component inhibitors, antibody-based compounds, and receptor antagonists, are in clinical trials or in preclinical evaluation [ 179 ]. While eculizumab, a humanized IgG antibody against complement component 5 (C5), seems to be ineffective in the management of dry AMD patients [ 180 ], treatment with lampalizumab, an antibody that inhibits complement factor D, reduced the progression of geographic atrophy lesion [ 181 ]. Since treatment with lampalizumab seems to be more effective in patients with specific CFI genotypes, a phase III trial is currently running.…”

Section: Implications For Preventive and Personalized Medicinementioning

confidence: 99%

Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

Maugeri

Barchitta

Mazzone³

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-candidate studies have been enabled to identify genetic variants in the complement system associated with AMD pathogenesis, the effect of gene-environment interaction is still under debate. In this review we provide an overview of the role of complement system and its genetic variants in AMD, summarizing the consequences of the interaction between genetic and environmental risk factors on AMD onset, progression, and therapeutic response. Finally, we discuss the perspectives of current evidence in the field of genomics driven personalized medicine and public health.

show abstract

Potential role of lampalizumab for treatment of geographic atrophy

Cited by 14 publications

References 28 publications

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

Recent developments in age-related macular degeneration: a review

Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

Contact Info

Product

Resources

About