TY - JOUR
T1 - Aqueous Cytokine Expression and Higher Order OCT Biomarkers
T2 - Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study
AU - Abraham, Joseph R.
AU - Wykoff, Charles C.
AU - Arepalli, Sruthi
AU - Lunasco, Leina
AU - Yu, Hannah J.
AU - Hu, Ming
AU - Reese, Jamie
AU - Srivastava, Sunil K.
AU - Brown, David M.
AU - Ehlers, Justis P.
N1 - Funding Information:
Funding/support: This work was supported by Regeneron, United States (REGE1901), an RPB unrestricted grant to the Cole Eye Institute (RPB1508DM), the National Institutes of Health, United States (K23 -EY022947), and the Betty J. Powers Retina Research Fellowship. Financial Disclosures: C.C.W. has received research support from Adverum, Allergan, Apellis, Clearside, EyePoint, Genentech/Roch, Neurotech, Novartis, Opthea, Regeneron, Regenxbio, Samsung, and Santen; has been a consultant for Alimera Sciences, Allegro, Allergan, Alynylam, Apellis, Bayer, Clearside, D.O.R.C. EyePoint, Genentech/Roche, Kodiak, Notal Vision, Novartis, ONL Therapeutics, PolyPhotonix, RecensMedical, Regeneron, Regenxbio, and Santen; and has been a speaker for Regeneron. S.K.S. has received research support from Regeneron, Allergan, and Gilead; and has been a consultant for Bausch and Lomb, Novartis, and Regeneron. D.M.B. has received research support from Adverum, Allergan, Apellis, Clearside, Genentech/Roche, Novartis, Opthea, Regeneron, Regenxbio, Samsung, and Santen; and has been a consultant for Regeneron, Bayer, Senju, Allergan, Optos, Zeiss, Heidelberg, OHR, Biotime, Gemini, Genentech/Roche, Novartis, Apellis, Regenxbio, and Chengdu Kanghong Biotechnology. J.P,E. has received research support from Aerpio, Alcon, Thrombogenics/Oxurion, Regeneron, Genentech, Novartis, and Allergan; has been a consultant for Aerpio, Alcon, Allegro, Allergan, Genentech/Roche, Novartis, Thrombogenics/Oxurion, Leica, Zeiss, Regeneron, and Santen; and holds a patent with Leica. The others authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Funding Information:
Funding/support: This work was supported by Regeneron, United States ( REGE1901 ), an RPB unrestricted grant to the Cole Eye Institute ( RPB1508DM ), the National Institutes of Health, United States ( K23 -EY022947 ), and the Betty J. Powers Retina Research Fellowship.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2
Y1 - 2021/2
N2 - Purpose: To identify biomarkers for predicting response to anti−vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. Design: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. Methods: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. Results: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (−24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = −0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). Conclusions: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
AB - Purpose: To identify biomarkers for predicting response to anti−vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. Design: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. Methods: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. Results: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (−24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = −0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). Conclusions: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
KW - Adult
KW - Aged
KW - Angiogenesis Inhibitors/administration & dosage
KW - Aqueous Humor/metabolism
KW - Biomarkers/metabolism
KW - Cytokines/biosynthesis
KW - Diabetic Retinopathy/diagnosis
KW - Female
KW - Humans
KW - Intravitreal Injections
KW - Macula Lutea/pathology
KW - Macular Edema/diagnosis
KW - Male
KW - Middle Aged
KW - Tomography, Optical Coherence/methods
KW - Vascular Endothelial Growth Factor A/antagonists & inhibitors
KW - Visual Acuity
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U2 - 10.1016/j.ajo.2020.08.047
DO - 10.1016/j.ajo.2020.08.047
M3 - Article
C2 - 32896498
AN - SCOPUS:85096985016
SN - 0002-9394
VL - 222
SP - 328
EP - 339
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -