Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema

A DRCR network phase 2 randomized clinical trial

Diabetic Retinopathy Clinical Research Network

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

IMPORTANCE Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. OBJECTIVE To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. DESIGN, SETTING, AND PARTICIPANTS Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. INTERVENTIONS Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. MAIN OUTCOMES AND MEASURES The primary outcomewas change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. RESULTS Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9%were female and 60.3%were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95%CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95%CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). CONCLUSIONS AND RELEVANCE Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01945866

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalJAMA Ophthalmology
Volume136
Issue number1
DOIs
StatePublished - Jan 1 2018

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Macular Edema
Dexamethasone
Randomized Controlled Trials
Vascular Endothelial Growth Factor A
Visual Acuity
Therapeutics
Intraocular Pressure
Ranibizumab
Injections
Ophthalmic Solutions
Optical Coherence Tomography
Diabetic Retinopathy
Clinical Protocols
Random Allocation
Antihypertensive Agents
Adrenal Cortex Hormones
Arm
Placebos

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema : A DRCR network phase 2 randomized clinical trial. / Diabetic Retinopathy Clinical Research Network.

In: JAMA Ophthalmology, Vol. 136, No. 1, 01.01.2018, p. 29-38.

Research output: Contribution to journalArticle

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title = "Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: A DRCR network phase 2 randomized clinical trial",
abstract = "IMPORTANCE Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. OBJECTIVE To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. DESIGN, SETTING, AND PARTICIPANTS Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. INTERVENTIONS Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. MAIN OUTCOMES AND MEASURES The primary outcomewas change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. RESULTS Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9{\%}were female and 60.3{\%}were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95{\%}CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95{\%}CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29{\%}) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). CONCLUSIONS AND RELEVANCE Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01945866",
author = "{Diabetic Retinopathy Clinical Research Network} and Maturi, {Raj K.} and Glassman, {Adam R.} and Danni Liu and Beck, {Roy W.} and Bhavsar, {Abdhish R.} and Bressler, {Neil M.} and Jampol, {Lee M.} and Michele Melia and Punjabi, {Omar S.} and Hani Salehi-Had and Sun, {Jennifer K.} and David Browning and Antoszyk, {Andrew N.} and Price, {Angela K.} and Herby, {Jenna T.} and Jones, {Taylor S.} and Fredenberg, {Sherry L.} and Courtney Mahr and Fleming, {Christina J.} and Ennis, {Sarah A.} and Erica Breglio and Karow, {Angella S.} and Jackson, {Lisa A.} and Balasubramaniam, {Uma M.} and Bojaj, {Swann J.} and Donna McClain and Lynn Watson and Clark, {Loraine M.} and Kathryn Kimrey and Kuopus, {Jeff A.} and Simchik, {Carol A.} and Rowland, {Beverly O.} and Finch, {Autumn K.} and McOwen, {Michael D.} and Sara Ahmed and Khodai, {Amy L.} and Stephanie Ramirez and Mireles, {Michael J.} and Mary Ma and Lee, {Scott F.} and Rivero, {Monica J.} and Lily Castillo and Harless, {Ashley M.} and Novak, {Carolee K.} and Nicole Ellingwood and Lorraine White and Alisha Ware and Weng, {Christina Y.} and Joseph Googe and Nicholas Anderson",
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T1 - Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema

T2 - A DRCR network phase 2 randomized clinical trial

AU - Diabetic Retinopathy Clinical Research Network

AU - Maturi, Raj K.

AU - Glassman, Adam R.

AU - Liu, Danni

AU - Beck, Roy W.

AU - Bhavsar, Abdhish R.

AU - Bressler, Neil M.

AU - Jampol, Lee M.

AU - Melia, Michele

AU - Punjabi, Omar S.

AU - Salehi-Had, Hani

AU - Sun, Jennifer K.

AU - Browning, David

AU - Antoszyk, Andrew N.

AU - Price, Angela K.

AU - Herby, Jenna T.

AU - Jones, Taylor S.

AU - Fredenberg, Sherry L.

AU - Mahr, Courtney

AU - Fleming, Christina J.

AU - Ennis, Sarah A.

AU - Breglio, Erica

AU - Karow, Angella S.

AU - Jackson, Lisa A.

AU - Balasubramaniam, Uma M.

AU - Bojaj, Swann J.

AU - McClain, Donna

AU - Watson, Lynn

AU - Clark, Loraine M.

AU - Kimrey, Kathryn

AU - Kuopus, Jeff A.

AU - Simchik, Carol A.

AU - Rowland, Beverly O.

AU - Finch, Autumn K.

AU - McOwen, Michael D.

AU - Ahmed, Sara

AU - Khodai, Amy L.

AU - Ramirez, Stephanie

AU - Mireles, Michael J.

AU - Ma, Mary

AU - Lee, Scott F.

AU - Rivero, Monica J.

AU - Castillo, Lily

AU - Harless, Ashley M.

AU - Novak, Carolee K.

AU - Ellingwood, Nicole

AU - White, Lorraine

AU - Ware, Alisha

AU - Weng, Christina Y.

AU - Googe, Joseph

AU - Anderson, Nicholas

PY - 2018/1/1

Y1 - 2018/1/1

N2 - IMPORTANCE Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. OBJECTIVE To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. DESIGN, SETTING, AND PARTICIPANTS Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. INTERVENTIONS Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. MAIN OUTCOMES AND MEASURES The primary outcomewas change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. RESULTS Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9%were female and 60.3%were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95%CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95%CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). CONCLUSIONS AND RELEVANCE Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01945866

AB - IMPORTANCE Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. OBJECTIVE To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. DESIGN, SETTING, AND PARTICIPANTS Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. INTERVENTIONS Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. MAIN OUTCOMES AND MEASURES The primary outcomewas change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. RESULTS Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9%were female and 60.3%were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95%CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95%CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). CONCLUSIONS AND RELEVANCE Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01945866

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