A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study)

Abstract

Objective To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata (PRN) Ozurdex treatment in patients with refractory diabetic macular oedema (DMO). Design Prospective, multicentre, randomized active-controlled non-inferiority clinical trial. Participants Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO. Interventions Participants were randomized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO. Data were collected on best-corrected visual acuity (BCVA), patient-reported outcome measures (PROM), macular thickness and morphology, diabetic retinopathy status, number of injections and adverse events from baseline for a period of 12 months. Main outcome measures The primary outcome was the difference between arms in change in BCVA from baseline to 12 months. The prespecified non-inferiority margin was five ETDRS letters. Key secondary outcomes included change in PROM scores, change in macular thickness, change in retinopathy and macular morphology, and safety profile. Results The mean change in BCVA was +1.48 (SD 14.8) in the fixed arm vs − 0.17 (SD 13.1) in the PRN arm, with adjusted effect estimate +0.97, 90% confidence interval (−4.01, +5.95), P = 0.02 (per protocol analysis). The conclusions of the ITT analysis were primarily supportive, − 0.34 (−5.49, 4.81) P = 0.07, but sensitive to an alternative assumption on missing data, +0.28 (−4.72, 5.27) P = 0.04. Conclusions The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis.

Health-related quality of life, visual function and treatment satisfaction following intravitreal dexamethasone implant for diabetic macular edema

“…To assess the PROMs in patients treated with dexamethasone intravitreal implant for refractory DME, as part of the OZDRY study,16 the following questionnaires were administered at screening and at the exit visit (month 12), prior to any intervention/treatment that may affect the patients’ response. Higher scores in these questionnaires at the exit visit compared to those at screening indicated better quality of life (QoL) and increased satisfaction.…”

“…We recently conducted the OZDRY study to compare two dosing regimens of dexamethasone intravitreal implant for chronic DME in terms of the conventional functional and anatomical outcomes of VA and retinal thickness and also to use standard questionnaire tools to explore and describe quantitatively patient-reported outcome measures (PROMs), which are infrequently reported from registration studies. The VA and retinal thickness data have been reported in a previous publication 16. In this second report from the OZDRY study, we describe the effect of two different regimens of dexamethasone intravitreal implant therapy for DME on PROMs and some baseline predictors of changes in PROMs using specific questionnaires, ie, the Visual Function Questionnaire-25 (VFQ-25), the Retinopathy-Dependent Quality of Life (RetDQoL) questionnaire and the Retinopathy Treatment Satisfaction Questionnaire (RetTSQ).…”

Diabetic macular oedema: evidence‐based treatment recommendations for Asian countries

“…The OZDRY study compared the effectiveness and safety of 5‐monthly fixed dosing with pro re nata dexamethasone (Ozurdex) treatment in patients with refractory DME. Based on a per protocol analysis, a 5‐monthly fixed dosing of dexamethasone was non‐inferior to optical coherence tomography (OCT)‐guided pro re nata therapy at 12 months (mean BCVA change: +1.48 ± 14.8 vs −0.17 ± 13.1, respectively; P = 0.02) . More recently, the OZLASE study examined the safety and clinical efficacy of combined repeated dexamethasone (Ozurdex) and macular laser therapy (MLT) compared with MLT monotherapy.…”

“…Based on a per protocol analysis, a 5-monthly fixed dosing of dexamethasone was non-inferior to optical coherence tomography (OCT)-guided pro re nata therapy at 12 months (mean BCVA change: +1.48 ± 14.8 vs À0.17 ± 13.1, respectively; P = 0.02). 58 More recently, the OZLASE study examined the safety and clinical efficacy of combined repeated dexamethasone (Ozurdex) and macular laser therapy (MLT) compared with MLT monotherapy. Despite a significant decrease in central subfield thickness, there was no significant difference in the visual outcomes of the two treatment arms at 56 weeks (combination arm, À0.3 ± 11.4 ETDRS letters; MLT monotherapy, +0.4 ± 9.6 ETDRS letters).…”

An Evidence-based Approach to Using Intravitreal Steroids in the Management of Diabetic Macular Oedema

“…36 There were 100 patients recruited into the study and randomised evenly between the two groups. The non-inferiority margin was pre-defined as <5 ETDRS letters difference.…”