The Effect of Systemic Levels of TNF-alpha and Complement Pathway Activity on Outcomes of VEGF Inhibition in Neovascular AMD
The Effect of Systemic Levels of TNF-alpha and Complement Pathway Activity on Outcomes of VEGF Inhibition in Neovascular AMD
Background/Objectives: Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD. Methods: Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD. Results: A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS. Conclusions: Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.
Age-Related Macular Degeneration, Complement;, Cytokines, Tumour Necrosis Factor-alpha, Vascular Endothelial Growth Factor
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Pierce, Charles
5705c4e1-86f6-49cb-80e7-9f58903d69f4
De Salvo, Gabriella
a747876b-c03d-4655-b31c-735e0f2920d2
Griffiths, Helen
a097fdaa-d3d6-49a9-9c69-0e6e5a5d518b
Nelson, Marie
cb6751b9-c0c3-4812-b050-5d615d152646
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Menon, Geeta
941f77e0-5d93-49a8-ac38-a250c4bdbc06
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
8 November 2021
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Pierce, Charles
5705c4e1-86f6-49cb-80e7-9f58903d69f4
De Salvo, Gabriella
a747876b-c03d-4655-b31c-735e0f2920d2
Griffiths, Helen
a097fdaa-d3d6-49a9-9c69-0e6e5a5d518b
Nelson, Marie
cb6751b9-c0c3-4812-b050-5d615d152646
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Menon, Geeta
941f77e0-5d93-49a8-ac38-a250c4bdbc06
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Khan, Adnan, Pierce, Charles, De Salvo, Gabriella, Griffiths, Helen, Nelson, Marie, Cree, Angela, Menon, Geeta and Lotery, Andrew
(2021)
The Effect of Systemic Levels of TNF-alpha and Complement Pathway Activity on Outcomes of VEGF Inhibition in Neovascular AMD.
Eye.
(doi:10.1038/s41433-021-01824-3).
Abstract
Background/Objectives: Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD. Methods: Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD. Results: A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS. Conclusions: Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.
Text
35601_2_merged_1633394031
- Accepted Manuscript
Text
s41433-021-01824-3
- Version of Record
More information
Accepted/In Press date: 4 October 2021
e-pub ahead of print date: 8 November 2021
Published date: 8 November 2021
Additional Information:
Funding Information:
This study was supported by an educational grant from Novartis UK.
Publisher Copyright:
© 2021, The Author(s).
Keywords:
Age-Related Macular Degeneration, Complement;, Cytokines, Tumour Necrosis Factor-alpha, Vascular Endothelial Growth Factor
Identifiers
Local EPrints ID: 451831
URI: http://eprints.soton.ac.uk/id/eprint/451831
ISSN: 0950-222X
PURE UUID: 4ce2534c-7a03-4d28-bc78-a7ad42e701c9
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Date deposited: 29 Oct 2021 16:30
Last modified: 17 Mar 2024 06:52
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Author:
Charles Pierce
Author:
Gabriella De Salvo
Author:
Helen Griffiths
Author:
Marie Nelson
Author:
Geeta Menon
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