Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Sep 17;14(9):990.
doi: 10.3390/jpm14090990.

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review

Ana Maria Dascalu  1   2 , Catalin Cicerone Grigorescu  3 , Dragos Serban  1   4 , Corneliu Tudor  1   4 , Cristina Alexandrescu  1   2 , Daniela Stana  2 , Sanda Jurja  5   6 , Andreea Cristina Costea  7 , Catalin Alius  1   4 , Laura Carina Tribus  8   9 , Dan Dumitrescu  1   4 , Dan Bratu  10   11 , Bogdan Mihai Cristea  1
Affiliations
Review

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review

Ana Maria Dascalu et al. J Pers Med. .

Abstract

Background/objectives: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases.

Methods: A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks.

Results: Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm2. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm2 in treated participants vs. 2.7 ± 0.8 mm2 in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline.

Conclusions: Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

Keywords: age-related macular degeneration; avacincaptad pegol; biomarkers; complement inhibitors; geographic atrophy; lampalizumab; outcomes; pegcetacoplan; personalized therapy.

PubMed Disclaimer

Conflict of interest statement

Andreea Cristina Costea of Diaverum Nephrology and Dialysis Clinic Constanta was involved in the software and review and editing of the manuscript. The remaining authors declare that they have no commercial or financial relationships that could be perceived as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart for the studies included in the review.
Figure 2
Figure 2
Effects of complement inhibitors vs. sham on BCVA change: Forrest plot—pooled effects–random effects model (MedCalc Software©). References [27,28,29,38,40,41].
Figure 3
Figure 3
Differences in the growth of the GA area during the follow-up period between the treated arms and the controls [26,28,29,38,40,41]. Color code: blue—lampalizumab; orange—pegcetacoplan; green—avacincaptad pegol; LM—lampalizumab monthly; LEOM—lampalizumab every other month; q4w—every 4 weeks; q6w—every 6 weeks; PM—pegcetacoplan monthly; PEOM—pegcetacoplan every other month.
Figure 4
Figure 4
Effects of intravitreal complement inhibitors vs. sham on GA area change. Forrest plots—pooled effects–random effects models: (a) for studies included in the meta-analysis [27,28,29,38,40,41]; (b) for pool results of the studies involving lampalizumab, pegcetacoplan, and avacincaptad pegol.
Figure 5
Figure 5
Targeting complement cascade for GA in AMD.
See this image and copyright information in PMC

References

    1. Wong W.L., Su X., Li X., Cheung C.M., Klein R., Cheng C.Y., Wong T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob. Health. 2014;2:e106–e116. doi: 10.1016/S2214-109X(13)70145-1. - DOI - PubMed
    1. Vision Loss Expert Group of the Global Burden of Disease Study. The GBD 2019 Blindness and Vision Impairment Collaborators Global estimates on the number of people blind or visually impaired by age-related macular degeneration: A meta-analysis from 2000 to 2020. Eye. 2024;38:2036–2046. doi: 10.1038/s41433-024-02995-5. - DOI - PMC - PubMed
    1. Bakri S.J., Bektas M., Sharp D., Luo R., Sarda S.P., Khan S. Geographic atrophy: Mechanism of disease, pathophysiology, and role of the complement system. J. Manag. Care Spec. Pharm. 2023;29((Suppl. 5-a)):S2–S11. doi: 10.18553/jmcp.2023.29.5-a.s2. - DOI - PMC - PubMed
    1. Varma R., Souied E.H., Tufail A., Tschosik E., Ferrara D., Zhang J., Silverman D., Dolan C., Bressler N.M. Maximum Reading Speed in Patients with Geographic Atrophy Secondary to Age-Related Macular Degeneration. Investig. Ophthalmol. Vis. Sci. 2018;59:AMD195–AMD201. doi: 10.1167/iovs.18-24238. - DOI - PubMed
    1. Evans J.R., Lawrenson J.G. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst. Rev. 2017;7:CD000254. doi: 10.1002/14651858.CD000254.pub4. - DOI - PMC - PubMed

LinkOut - more resources