Factors Associated with Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema with Anti-Vascular Endothelial Growth Factor Therapy: An Exploratory Analysis of the Protocol T Randomized Clinical Trial

Susan B Bressler, Isoken Odia, Maureen G. Maguire, Dilsher S. Dhoot, Adam R. Glassman, Lee M. Jampol, Dennis M. Marcus, Sharon Solomon, Jennifer K. Sun

Research output: Contribution to journalArticle

Abstract

Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial, Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P <.001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P <.001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P <.001) and 0.5 letters (95% CI, -0.9 to -0.2; P <.001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P =.007) and VA AUC (95% CI, 1.3-4.2; P <.001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P =.01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P =.01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

Original languageEnglish (US)
JournalJAMA Ophthalmology
DOIs
StateAccepted/In press - Jan 1 2019

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Macular Edema
Vascular Endothelial Growth Factor A
Visual Acuity
Randomized Controlled Trials
Light Coagulation
Area Under Curve
Therapeutics
Optical Coherence Tomography
Diabetic Retinopathy
Clinical Protocols
Hemoglobins
Subretinal Fluid
African Americans

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Factors Associated with Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema with Anti-Vascular Endothelial Growth Factor Therapy : An Exploratory Analysis of the Protocol T Randomized Clinical Trial. / Bressler, Susan B; Odia, Isoken; Maguire, Maureen G.; Dhoot, Dilsher S.; Glassman, Adam R.; Jampol, Lee M.; Marcus, Dennis M.; Solomon, Sharon; Sun, Jennifer K.

In: JAMA Ophthalmology, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial, Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95{\%} CI, -3.0 to -1.2; P <.001) in the VA and 1.9 letters (95{\%} CI, -2.4 to -1.3; P <.001) in the VA AUC analyses. For each 1{\%} increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95{\%} CI, -1.5 to -0.5; P <.001) and 0.5 letters (95{\%} CI, -0.9 to -0.2; P <.001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95{\%} CI, 0.9-5.4; P =.007) and VA AUC (95{\%} CI, 1.3-4.2; P <.001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P =.01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P =.01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.",
author = "Bressler, {Susan B} and Isoken Odia and Maguire, {Maureen G.} and Dhoot, {Dilsher S.} and Glassman, {Adam R.} and Jampol, {Lee M.} and Marcus, {Dennis M.} and Sharon Solomon and Sun, {Jennifer K.}",
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TY - JOUR

T1 - Factors Associated with Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema with Anti-Vascular Endothelial Growth Factor Therapy

T2 - An Exploratory Analysis of the Protocol T Randomized Clinical Trial

AU - Bressler, Susan B

AU - Odia, Isoken

AU - Maguire, Maureen G.

AU - Dhoot, Dilsher S.

AU - Glassman, Adam R.

AU - Jampol, Lee M.

AU - Marcus, Dennis M.

AU - Solomon, Sharon

AU - Sun, Jennifer K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial, Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P <.001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P <.001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P <.001) and 0.5 letters (95% CI, -0.9 to -0.2; P <.001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P =.007) and VA AUC (95% CI, 1.3-4.2; P <.001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P =.01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P =.01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

AB - Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial, Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P <.001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P <.001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P <.001) and 0.5 letters (95% CI, -0.9 to -0.2; P <.001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P =.007) and VA AUC (95% CI, 1.3-4.2; P <.001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P =.01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P =.01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

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