Joseph R Abraham1, Charles C Wykoff2, Sruthi Arepalli3, Leina Lunasco1, Hannah J Yu4, Ming Hu5, Jamie Reese1, Sunil K Srivastava3, David M Brown2, Justis P Ehlers6. 1. Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. 2. Retina Consultants of Houston, Retina Consultants of America, Houston, Texas, USA; Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA. 3. Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. 4. Retina Consultants of Houston, Retina Consultants of America, Houston, Texas, USA. 5. Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA. 6. Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: ehlersj@ccf.org.
Abstract
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.
RCT Entities:
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.
Authors: Sruthi Arepalli; Charles C Wykoff; Joseph R Abraham; Leina Lunasco; Hannah Yu; Ming Hu; Sunil K Srivastava; Jamie L Reese; David Brown; Justis P Ehlers Journal: Eye (Lond) Date: 2022-10-11 Impact factor: 4.456
Authors: Marion R Munk; Gabor Mark Somfai; Marc D de Smet; Guy Donati; Marcel N Menke; Justus G Garweg; Lala Ceklic Journal: Int J Mol Sci Date: 2022-07-08 Impact factor: 6.208
Authors: Sudeshna Sil Kar; Joseph Abraham; Charles C Wykoff; Duriye Damla Sevgi; Leina Lunasco; David M Brown; Sunil K Srivastava; Anant Madabhushi; Justis P Ehlers Journal: Ophthalmol Sci Date: 2022-02-04
Authors: Joseph R Abraham; Charles C Wykoff; Sruthi Arepalli; Leina Lunasco; Hannah J Yu; Alison Martin; Christopher Mugnaini; Ming Hu; Jamie Reese; Sunil K Srivastava; David M Brown; Justis P Ehlers Journal: Br J Ophthalmol Date: 2021-06-07 Impact factor: 5.908
Authors: Sudeshna Sil Kar; Duriye Damla Sevgi; Vincent Dong; Sunil K Srivastava; Anant Madabhushi; Justis P Ehlers Journal: IEEE J Transl Eng Health Med Date: 2021-07-12