Intravitreal Ranibizumab Versus Its Combination With Dexamethasone in The Treatment of Diabetic Macular Edema

Study Overview
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Brief Summary
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Intravitreal ranibizumab alone was Compared to adding dexamethasone to ranibizumab regarding central macular thickness, the visual acuity and the number of intravitreal injections needed to achieve the same effect on CMT and BCVA at the end of the 6 months duration of the study. Any significant change in final IOP, compared to baseline, in either group is reported.

Detailed Description
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This prospective randomized study measures the changes in central macular thickness, best corrected visual acuity and IOP in diabetic macular edema before and after the intravitreal injection of ranibizumab and dexamethasone, compared to ranibizumab alone, the current gold standard of care for diabetic macular edema. Study participants were randomized into 2 groups: the first group received 3 Intravitreal injections of ranibizumab alone 1 month apart. While the second group received 1 Intravitreal injection of a combination of ranibizumab and 0.4 mg in 0.1 ml dexamethasone followed by 2 Intravitreal ranibizumab, 1 month apart (with dexamethasone if follow up OCT shows less than 10% improvement from baseline). Treatment was stopped when the treated eye achieved a central macular thickness of 250 microns or less with no focal parafoveal edema. Final recorded central macular thickness in both groups compared to the baseline. By the end of the follow up period. Final visual acuity was assessed in both groups compared to the baseline Change in final IOP, compared to baseline, in ranibizumab group and ranibizumab with dexamethasone group. . The number of injections needed to achieve the same effect on CMT and BCVA.

Official Title
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Comparative Study of the Efficacy of Intravitreal Ranibizumab Versus Its Combination With Commercial Dexamethasone in The Treatment of Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Lucentis alone group
* Drug: Lucentis dexamethasone group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetic macular edema with central macular thickness of 300 μm or greater (as measured by spectral domain optical coherence tomography [OCT]). Best corrected visual acuity of 6/12 or less. Exclusion Criteria: ● History of any treatment for DME (including grid or focal laser photocoagulation) within the last 6 months History of panretinal photocoagulation within the last 6 months. PDR as indicated with Fluorescein Angiography as it will require PRP which may affect DME. Macular ischemia, as indicated with Fluorescein Angiography. Cataract surgery within three months or cataract that requires surgical intervention during the follow-up period. Pseudophakia with Irvine Gass syndrome, as indicated with Fluorescein Angiography. Vitreomacular traction syndrome. Other causes of macular edema (eg. CRVO, CNV, uveitis, etc). Glaucoma, whether suspected or confirmed. Significant media opacity. Patients with ocular or periocular infections, or infection in the other eye Signs of Active or resolved uveitis and intraocular inflammation. Bad diabetic control as indicated by HbA1C >8. Renal impairment, hepatic impairment, or congestive heart failure. History of cardiovascular insult or stroke.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The first group received 3 monthly intravitreal injections of 0.5 mg in 0.05 mL ranibizumab alone (Lucentis, by Novartis), aspirated from vial through 5-micron sterile filter needle (19-gauge × 1-1/2 inch), with a 1-mL syringe and injected through a 30-gauge × ½ inch sterile injection needle. While the second group received monthly intravitreal injections of the same dose of ranibizumab combined with 0.4 mg in 0.1 ml dexamethasone (Dexamethasone sodium phosphate, Amriya Pharmaceuticals, Cairo, Egypt) in a separate 1ml syringe with 27- gauge × ½ inch sterile injection needle, followed by 2 Intravitreal ranibizumab, 1 month apart (with dexamethasone if follow up OCT shows less than 10% improvement from baseline i.e., PRN).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: The first group, Lucentis alone group<br>The first group received 3 monthly intravitreal injections of 0.5 mg in 0.05 mL ranibizumab alone (Lucentis, by Novartis), aspirated from vial through 5-micron sterile filter needle (19-gauge × 1-1/2 inch), with a 1-mL syringe and injected through a 30-gauge × ½ inch sterile injection needle. | Drug: Lucentis alone group<br>* The Lucentis alone group received 3 monthly intravitreal injections of lucentis alone or less than 3 injections if the central foveal thickness reached 250 microns<br>|
| Active Comparator: The second group, Lucentis dexamethasone group<br>The second group received monthly intravitreal injections of the same dose of ranibizumab combined with 0.4 mg in 0.1 ml dexamethasone (Dexamethasone sodium phosphate, Amriya Pharmaceuticals, Cairo, Egypt) in a separate 1ml syringe with 27- gauge × ½ inch sterile injection needle, followed by 2 Intravitreal ranibizumab, 1 month apart (with dexamethasone if follow up OCT shows less than 10% improvement from baseline i.e., PRN). | Drug: Lucentis dexamethasone group<br>* Lucentis dexamethasone group received intravitreal injections of combination of both lucentis and commercial dexamethasone. the second group received monthly intravitreal injections of the same dose of ranibizumab combined with 0.4 mg in 0.1 ml dexamethasone (Dexamethasone sodium phosphate, Amriya Pharmaceuticals, Cairo, Egypt) in a separate 1ml syringe with 27- gauge × ½ inch sterile injection needle, followed by 2 Intravitreal ranibizumab, 1 month apart (with dexamethasone if follow up OCT shows less than 10% improvement from baseline i.e., PRN). Treatment was stopped when CMT improved below 250 µ.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central foveal thickness | Central foveal thickness in microns measured by OCT | 6 months after the first injection | 
| BCVA (Decimal) | Best corrected visual acuity measured on Snellen chart in Decimal form | 6 months after the first injection | 
| The number of injections | The total number of injections in each Arm group | over 6 months duration of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IOP | Intraocular pressure | 6 months after the first injection |