Background This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME).
Methods The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response.
Results Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05).
Conclusions Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.
- aqueous humour
Data availability statement
Data are available upon reasonable request.
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Contributors JRA: formal analysis, investigation, writing (original draft) and project administration. CCW: resources, investigation, supervision, writing (review and editing). SA: formal analysis and writing (review and editing). LL: formal analysis, investigation, project administration and writing (review and editing).HJY: investigation and writing (review and editing). AM: formal analysis. CM and MH: formal analysis. JR: supervision and project administration. SKS: resources and writing (review and editing). DMB: resources, investigation and writing (review and editing. JPE: conceptualisation, resources, methodology, software, writing (review and editing), supervision, project administration and funding acquisition.
Funding JPE: RPB Unrestricted Grant to the Cole Eye Institute. RPB1508DM; NIH K23-EY022947. Regeneron REGE1901JE; JRA: Betty Powers Retina Research Fellowship. No associated grant number. The funding organisations and sources had no role in the design or conduct of this research.
Competing interests JRA, SA, LL, HJY, MH, JR: none; CCW, Adverum (research funding (F)), Alimera Sciences (consultant (C)) Allergan (C, F), Allegro (C), Apellis (C, F), Alynylam (C), Bayer (C), Clearside (C, F), DORC (C), EyePoint (C, F), Genentech/Roche (C, F), Kodiak (C), Neurotech (F), Notal Vision (C), ONL Therapeutics (C), Novartis (C, F), Polyphontonix (C), Regeneron (C, F, S), Regenxbio (C, F), Samsung (F), Santen (C, F); SKS: Regeneron (F), Allergan (F), Gilead (F), Bausch and Lomb (C), Santen (C), Leica (patent (P)); DMB, Adverum (F) Allergan (C, F), Apellis (F), Bayer (C), Biotime (C), Clearside (F), Chengdu Kanghong Biotechnology (C), Gemini (C), Genentech/Roche (C, F), Heidelberg (C), Novartis (C, F), OHR (C), Opthea (F), Optos (C), Zeiss (C), Regeneron (C, F), Regenxbio (C, F), Samsung (F), Santen (C), Senju (C); JPE: Aerpio (C, F), Alcon (C, F), Thrombogenics/Oxurion (C, F), Regeneron (C, F), Genetech (C, F), Novartis (C,F), Allergan (C, F), Roche (C), Leica (C, P), Zeiss (C), Santen (C).
Provenance and peer review Not commissioned; externally peer reviewed.
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