Intravitreal Ranibizumab or Aflibercept After Bevacizumab in Diabetic Macular Edema

Study Overview
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Brief Summary
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PURPOSE: To evaluate the efﬁcacy of switching from bevacizumab to ranibizumab (Lucentis; Genentech, South San Francisco, CA) or aflibercept (Eylea; Regeneron, Tarrytown, NY) in eyes with diabetic macular edema (DME) nonresponders to bevacizumab (Avastin; Genentech, South San Francisco, CA). METHODS: Single-center retrospective comparative study of patients with DME unresponsive to intravitreal bevacizumab that were switched to ranibizumab or aflibercept. Best-corrected visual acuity and central foveal thickness will be analysed prior to and 3 months after the switch. OCT biomarkers will also analyzed. A p value of 0.05 or less will be considered to be statistically significant. HYPOTHESIS: Patients will improve anatomically and functionally after switch.

Official Title
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Intravitreal Ranibizumab or Aflibercept After Bevacizumab in Diabetic Macular Edema

Conditions
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Diabetic Macular Edema, Diabetic Retinopathy

Intervention / Treatment
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* Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]
* Drug: Aflibercept 40 MG/ML Intraocular Solution [EYLEA]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 1 or type 2 diabetes mellitus patients older than 18 years with center-involved DME, defined as central subfield thickness (CST) of more than 300 µm on spectral-domain OCT (SD-OCT). nonresponsive to bevacizumab, deﬁned as having persistent intraretinal and/or subretinal fluid on optical coherence tomography (OCT), i.e CSF>300µm after a minimum of 3 monthly injections, 4 months before switch, regardless of visual acuity (VA). Exclusion Criteria: additional ocular diseases that could significantly affect the visual acuity such as: significant vitreoretinal interface abnormality on SD-OCT that may contribute to macular edema age-related macular degeneration retinal vascular occlusion central corneal opacity amblyopia advanced glaucoma optic neuropathy history of ocular trauma or surgery other than uncomplicated cataract extraction cataract surgery within 3 months before or after bevacizumab switch unable to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ranibizumab<br>Patients nonresponsive to bevacizumab that were switched to ranibizumab | Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]<br> <br> |
| aflibercept<br>Patients nonresponsive to bevacizumab that were switched to aflibercept | Drug: Aflibercept 40 MG/ML Intraocular Solution [EYLEA]<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anatomical change | The central foveal thickness (CFT), measured by Optical Coherence Tomography, was automatically measured by the software in the central 1 mm. A CFT <250 µm or >300 µm is considered pathological. A CFT between 200 and 300 µm is considered physiological. CFT has no defined minimum or maximum values. Since patients with diabetic macular edema usually have CFT >300 µm the goal of treatment is to lower the CFT to values between 200 and 300 µm. A clinical significant anatomical improvement was considered for a change in CFT≥10%. | Immediately before switch (one month after last bevacizumab intravitreal injection); 4 months after switch. Minimum of three intravitreal injections before and after switch. | 
| Functional change | Functional change was measure by the Early Treatment Diabetic Retinopathy Scale (ETDRS) which measures the best-corrected visual acuity with an ETDRS-like chart at 4 meters in number letters or at 1 meter when patients are unable to read any letters on the ETDRS chart at 4 meters. The ETDRS scale varies from 1 to 85 letters (85 letters correspond to a 20/20 in the Snellen scale). The higher the value the better the outcome. A clinical significant functional improvement was considered for a gain of ≥5 EDTRS letters. | Immediately before switch (one month after last bevacizumab intravitreal injection); 4 months after switch. Minimum of three intravitreal injections before and after switch. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema, Bevacizumab, Ranibizumab, Aflibercept, BCVA, OCT