The BIOMAC-Study: Modulation of CNV Activity in Neovascular AMD and Anti-VEGF Treatment Need Through Systemic Factors
Purpose
Inflammation and angiogenesis are the key pathophysiological mechanisms of neovascular age-related macular degeneration (nAMD). Both mechanisms are not specific to the eye, yet general mechanisms of the organism. The BIOMAC study investigated the influence of systemic factors on nAMD in a multi-omics approach.
Methods
BIOMAC included 46 nAMD subjects. Twenty-one had well controlled choroidal neovascularization (CNV) under anti-VEGF treatment (LF-group). In the remaining 25, CNV activity was poorly controlled despite injections every 4-6 weeks (HF-group). Proteomic profiles in blood samples were determined by LC-MS/MS mass spectrometry. Exploratory criteria were applied to identify potential candidate factors determining CNV activity. In addition, a non-linear classification model was applied after dimensionality reduction.
Results
Both strata were well balanced regarding age, gender, and BCVA (HF 61.4±15.7; LF 65.0±12.4). On an exploratory level, six proteins were up- and 3 downregulated in HF vs. LF. Up-regulated proteins: complement c1q subcomponent subunit b (ratio HF/LF=1,84; nominal p=0.0068), cytosol aminopeptidase (ratio HF/LF=1.54; nominal p=0.0318), and insulin-like growth factor-binding protein 3 (ratio HF/LF=4.1496; nominal p=0.0106). Down-regulated proteins: Acidic leucine-rich nuclear phosphoprotein 32 family member A (ratio HF/LF=0.67; nominal p=0.0482). The non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining nAMD course.
Conclusion
The data suggest a complex dependency of CNV activity from blood proteomic factors. Peripheral blood proteome may serve as a biomarker in future.
Conflict of interest
Yes
Details of conflicting interests
The First Author declares the following: The presented study was funded by Novartis. Consultant for Bayer, Novartis, Allergan, Omeicos, Oxular, SamChungDan Pharma, Boehringer Ingelheim; Grant support from Bayer, Novartis, Boehringer Ingelheim; Speaker honorarium from Allergan, Bayer, Novartis, Roche
Authors 1
Last name
ZEITZ
Initials of first name(s)
O
Department
Charité Universitätsmedizin Berlin, Dept. of Ophthalmology
City
Berlin
Country
Germany
Authors 2
Last name
Künzel
Initials of first name(s)
SE
Department
Charité Universitätsmedizin Berlin, Dept. of Ophthalmology
City
Berlin
Country
Germany
Authors 3
Last name
Knecht
Initials of first name(s)
VA
Department
Charité Universitätsmedizin Berlin, Dept. of Ophthalmology
City
Berlin
Country
Germany
Authors 4
Last name
Joussen
Initials of first name(s)
AM
Department
Charité Universitätsmedizin Berlin, Dept. of Ophthalmology
City
Berlin
Country
Germany
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